Animal Contact Outbreak Surveillnace System (CDC). National Outbreak Reporting System (NORS-CDC)
Generally
Enterobacteriaceae are the largest group of medically important bacteria which comprise a family of Gram negative rods that mostly inhabit the intestinal tract. The port of entry into the human body is usually orally.
Many enterics are harmless gut commensals or opportunists. However, some are pathogens (e.g., E coli which can cause bloody diarrhea, Klebsiella pneumoniae which can cause various types of pneumonia, Proteus mirabilis which can cause urinary tract infections, Salmonella tryphi which can cause typhoid fever, Shigella dysenteriae which can cause bacillary dysentery and Yersinia pestis which can cause the plague.
Each year, infections from major foodborn pathogens are responsible for an estimated 9.4 million illnesses, 56,000 hospitalization and 1,350 deaths in the U.S. To evaluate progress toward prevention of enteric infections in the US, the Foodborn Diseases Active Surveillance Network (FoodNet) conducts surveillance for laboratory-diagnosed infections causes by eith pathogens transmitted commonly through food at 10 U.S. sites. Campylobacter and Salmonella are the leading causes of bacterial enteric infections transmitted commonly by food. During 2022, FoodNet identified higher incidences of Shiga toxin-producing Escherichia coli, Yersinia, Vibrio and Cyclospora infections compared with 2016-2018. See CDC
An estimated 450k enteric illnesses, 5k hospitalization and 76 deaths assocaited with animal contact occur each year in teh US. Humans might encounter animal feces or bodily fluids thorugh contact wi the animal, its environment, food or water. Salmonella was the most common casue. Cryptosporidium was the second leading cuse.
Detection and Isolation
Example: Frm a carbapenemas proudcing enterobacterales (CPE) surveillance specimen, asthe stool specimen was inoculated on CHROMID CARBA SMART agar. The next day, scant gray colonies grew on the OXA side of the plate. The organism was identified as E. coli by matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectromety (Bruker Daltonics). owever, becasue the colonies were gray, not pink on the agar, and du to a known limitation that MALDI_TOF cannot distinguish E. coli from Sigella, serotyping uisng Shigella antisera and biochemical reactions were set up. Kligler ion agar was alkaline over acid with no H2S and produced litttle gas The organisms was negative for lysine, ornithin, indole and citrate. Motolity was negative, and the isolate showed agglutination with S. Flexneri group B antisera, types 1-6, and no agglutination with antisera for other Sigella groups. The identification was confirmed by the BD Phoenix system, which gave a 99% S. Flexneri identificaiton of the isolate. The isolate was forwarded to the Provincial laboratory and was serotyped as S. fleneri type 2a. Stool culture ordered as a reflex test after detection of Shigella species was multiplex PCR identified the organism when it grew as non-lactose fermenting colonies on MacConkey agar. DNA was extracted from an overnight culture of the bacterial isolate using the easyMag system (bioMerieux). Pufified DNA was prepared for sequencing using the Rapid Barcoding Sequencing Kit SQK-LSK114 (Oxford Nanopore Technologies, UK). Sequencing occurred on a GridION system using a R10.4.1 flow cell FLO-MIN114, Oxford Nanopore Technologies) with High-accuracy model basecalling with data captured over 26 hours. Data was evaluted with the MinKNOW software 23.04.5. A consensus genome was constructed using Flye 2.9. The consensus genome for botht he bacterial isoalte and plasmid were anlzyed thorugh the Reistance Gene Identificaiton tool within the Comprehensive Antibiotic Resistance Database. Hits demosntrating a greater than 95% identity and 95% lenght of reference sequence were included in analysis. The database identified 5 reistance genes present within the plasmid. The plasmid consensus sequence was visualized and annotated using Geneious Prime v2023.0.1 (Biomaters, US). “Detection of OXA-181 carbapenemase in Shigella flexneri”
1. Selective Media
MacConkey Agar: See outline
Eosin Methylene Blue Agar: See outline
Hektoen Enteric Agar: See outline
Major characteritiscs are the following:
- Growth on MacConkey agar: See differential media right hand column
- Gram negative rods
- Oxidase negative but most are catalase-positive
- acid production from glucose (with or without gas)
- Most reduce NO3 to NO2
2. Serological Classification
The serologic classification of Enterobacteriaceae is based on 3 major groups of antigens: somatic O LPS, capsular K antigens, and the flagellar H proteins. For example. “E. coli O157:H7” refers to the O antigen and flagellar protein.
One protocol might be to conduct whole-genome sequencing by extracting DNA using easyMag (bioMerieux), sequencing on a GridION system with a R10.4.1 flow cell (oxform nanopore Technologies) and analyzaing the data with MinKNOW 23.04.5 (oxform Nanopore Technologies) to construct a consensus genome using multiplex assay.
SeeGene Allplex GI-EB gastrointestinal multiplex assay
3. Antibody Susceptibility Testing:
Comprehensive Antibiotic Resistance Database
Specific Types of Enterobacteriaceae
Some members of this family like E coli and K. pneumonia are part of the normal bowel flora that can cause opportunistic infections whereas others like Salmonella, Shigella and Yersinia are always associated with disease. Virulence factors include –endotoxins, –capsules, –antigenic phase variation and –antimicrobial resistance.
P. mirabilis is capable of causing symptomatic infections of the urinary tract including cystitis and pyelonephritis and is present in cases of asymptomatic bacteriuria, particularly in the elderly and patients with type 2 diabetes. These infections can also cause bacteremia and progress to potentially life-threatening urosepsis. Additionally, P. mirabilis infections can cause the formation of urinary stones (urolithiasis).
Escherichia coli
E. coli are part of the normal flora. E coli and other “coliforms” are commonly found only in the bowel. (coliforms are used as a public health indicator of fecal contamination of water). They are facultative anaerobe, gram-negative rods and lactose positive fermentators. Most infections are endogenous (come from the gut and get into other parts of the body that they should not be in).
Escherichia coli: are gram-negative, facultative anaerobic, rod shaped bacteria which are often found in the lower intestinal tract of warm blooded animals as part of the natural flora. Some serotypes can cause serious food poisening in humans. The fecal-oral route is the major route through which pathogenic strains cause disease. It is one of the most widely studied prokaryotic organisms and has an important role in recombinant DNA. E coli can be distinguished from other coliforms (rod-shaped gram-negative non-spore forming bacteria which can ferment lactose and commonly used to indicate sanitary quality of foods and water) by the ability to ferment lactose at 44C in the fecal coliform test. See WHO
Metabolism:
Aerobic bacteria differ from anaerobic bacteria in their type of metabolism. They use different catabolic and, in some instances, anabolic pathways. Facultatively anaerobic bacteria must be capable of both types of metabolism. Facultative bacteria have developed elaborate mechanisms that permit the expression of the pathways only if required.
Escherichia coli, oxygen-regulated expression of the metabolic enzymes is effected by the transcriptional regulators ArcA (aerobic respiratory control) and FNR (fumarate and nitrate reductase regulation). The sensory protein kinase ArcB of the two-component ArcB/ ArcA system (Iuchi and Lin, 1993) is located in the cytoplasmic membrane and senses oxygen in an unknown mode, possibly via an intermediate of aerobic or anaerobic metabolism. The oxygen-sensing domain of FNR contains a surface-exposed Fe–S cluster, which is likely to undergo oxidation or reduction reactions, resulting in a functional change in FNR. A surface-exposed Fe–S cluster is expected to react with cellular reductants, for example glutathione or thiol proteins, such as thioredoxin or glutaredoxin. See Unden
Types:
–Enterohemorrhagic E. coli (EHEC) causes a Shiga-like toxin which causes bloody diarrhea. Enterotoxigenic E. coli (ETEC) causes traveler’s diarrhea and produces heat labile and heat stable enterotoxins similar to cholera which causes essential metabolites to flow out of the cell rather than into it. Together with group B streptococci, they are the most common cause of neonatal meningitis. They are also the most common gram negative organisms in septic patients. Virulence factors of pathogens include –adhesins, –exotoxins, –alpha hemolysins (which disrupt plasma membranes) and siderophores (which bind necessary ion).
Multidrug Resistance/Horizontal gene transfer:
Multidrug resistance in Escherichia coli has become a worrying issue that is increasingly observed in human but also in veterinary medicine worldwide. E. coli is intrinsically susceptible to almost all clinically relevant antimicrobial agents, but this bacterial species has a great capacity to accumulate resistance genes, mostly through horizontal gene transfer. The most problematic mechanisms in E. coli correspond to the acquisition of genes coding for extendeds pectrum β-lactamases (conferring resistance to broad-spectrum cephalosporins), carbapenemases (conferring resistance to carbapenems), 16S rRNA methylases (conferring pan-resistance to aminoglycosides), plasmid-mediated quinolone resistance (PMQR) genes (conferring resistance to [fluoro]quinolones), and mcr genes (conferring resistance to polymyxins). Although the spread of carbapenemase genes has been mainly recognized in the human sector but poorly recognized in animals, colistin resistance in E. coli seems rather to be related to the use of colistin in veterinary medicine on a global scale. For the other resistance traits, their cross-transfer between the human and animal sectors still remains controversial even though genomic investigations indicate that extended-spectrum β-lactamase producers encountered in animals are distinct from those affecting humans. In addition, E. coli of animal origin often also show resistances to other-mostly older-antimicrobial agents, including tetracyclines, phenicols, sulfonamides, trimethoprim, and fosfomycin. Plasmids, especially multiresistance plasmids, but also other mobile genetic elements, such as transposons and gene cassettes in class 1 and class 2 integrons, seem to play a major role in the dissemination of resistance genes. See Schwartz
Enterobacter aerogenes:
Enterobacter aerogenes is a gram negative oxidase negative, catalase positive, citrate positive, indole negative, rod-shaped bacterium. They are found in the gastroinestinal tract and are opportunistic bacteria.
Klebsiella pneumoniae
Klebsiella pneumoniae (K. pneumoniae) is a gram‐negative and non‐motile bacterium and belongs to Enterobacteriaceae, which was first described by Carl Friedlander in 1882 as a bacterium and isolated from the lungs of patients who had died of pneumonia. K. pneumoniae is ubiquitously found in water, soil, humans, and animals and can colonize healthcare‐related sites. K. pneumoniae could colonize a variety of sites in human body, for example, axilla, intestinal tract, and nasopharynx.
K. pneumoniae, a member of the Enterobacteriaceae family, has long been recognized as a formidable human pathogen associated with a wide range of infections, including urinary tract infections, pneumonia, bloodstream infections, and surgical site infections. The clinical significance of K. pneumoniae is underscored by its ability to exploit an array of virulence factors that facilitate adherence, colonization, and evasion of the host immune response. These virulence factors include capsule polysaccharides, lipopolysaccharides, fimbriae, and siderophores. Notably, the polysaccharide capsule confers resistance to phagocytosis and complements bacterial virulence by facilitating biofilm formation and mediating adherence to host tissues.
Klebsiella pneumoniae usually infects immunosuppressed individuals and cause a bloody sputum. They have an anti-phagocytic capsule. Carbapenem-resistant Enterobacteriaceae (CRE) are considered an urgent threat in the United States because they are associated with high morbidity and mortality, limited treatment options, and potential for rapid spread among patients. Carbapenemases, enzymes that confer resistance to the carbapenem class of antibiotics, are believed to contribute to increasing transmission and regional spread of CRE because the genes encoding these enzymes can reside on mobile plasmids and can be transferred among bacterial species. Klebsiella pneumoniae carbapenemase (KPC) is the most common carbapenemase seen in the United States, but isolates with the New Delhi metallo-β-lactamase (NDM) are emerging. Known risk factors for carbapenemase-producing CRE, including NDM, include health care exposures such as hospitalization outside the United States, recent overnight admissions to short-stay and long-term acute care hospitals, residence in long-term care facilities, surgical procedures, and having indwelling devices. Community-associated CRE lack these health care exposures and are rare in the United States. During 2014–2016, NDM-producing CRE were isolated from patients in Colorado without known health care risk factors. See CDC
Klebsiella pneumoniae is an encapsulated, non-motile Gram (−) bacillus that may inhabit the mammalian gastrointestinal tract as a commensal or a pathogen. Classical K. pneumoniae (cKP) infiltrates the urinary tract, bloodstream, lungs, and surgical wounds, leading to urinary tract infections, bacteremia, sepsis, pneumonia, and wound infections, primarily in healthcare settings. It is challenging to treat patients infected with cKp, because it tends to acquire multiple antibiotic resistances, including to carbapenems, cephalosporins, and monobactams, from the production of extended-spectrum β-lactamases and/or carbapenemases.
–Capsule polysaccharide (CPS) is among the most important virulence factors of Klebsiella pneumoniae. CPS prevents K. pneumoniae from phagocytosis, rendering the encapsulated strain more difficult to be eradicated by the host.
Among the known virulence factors of K. pneumoniae, CPS is considered the most important. The presence of a thick capsule at the cell surface protects K. pneumoniae from opsonization and phagocytosis by macrophages, DCs, neutrophils, and epithelial cells, by blocking the binding and internalization processes. CPS of K. pneumoniae also confers resistance to antimicrobial peptides. As a protective shield, CPS can limit the access of antimicrobial peptides to the bacterial cell. Moreover, sub-lethal concentrations of antimicrobial peptides in the airway induce cps gene expression, which, in turn, protects the bacteria against the action of antimicrobial polypeptides. CPS also suppresses the early inflammatory response of the host by reducing IL-8 expression through inhibiting TLR2 and TLR4 signaling and NOD1-dependent pathways. The virulence potential of K. pneumoniae is mainly determined by the capsule type rather than the amount of CPS. More than 79 capsular serotypes have been reported to date, with significant differences in virulence level being observed among different capsular types, of which K1 and K2 strains were found to be particularly virulent in a mouse peritonitis model. It has also been shown that phagocytosis of K. pneumoniae is partially mediated by LOX-1, a scavenger receptor of the host, and that CPS may impede interaction between LOX-1 and this pathogenic bacteria, therefore reducing the phagocytosis process. LOX-1 receptor mediates the internalization of K. pneumoniae, and CPS prevents this interaction possibly by providing a protective layer on the surface of bacteria, likely preventing exposure of proteins like GroEL and OmpA. This is one of the reasons why CPS helps K. pneumoniae escape phagocytosis. (liu “Capsular polysaccharide enables Klebsiella pneumoniae to evade phagocytosis by blocking host-bacteria interactions” Microbial Pathogenesis, March 2025 Volume 16 Issue 3)
–Siderophores: Iron is an essential redox-active cofactor in many biochemical reactions and bioenergetic pathways of pro- and eukaryotes. However, Fe3+ precipitates in aqueous environments, and eukaryotes sequester it. Mammalian iron-binding and storage proteins [siderocalin (SCN), transferrin, lactoferrin, and ferritin] minimize the amount of free iron available to invading microorganisms. Consequently, both commensal and pathogenic bacteria produce small organic chelators, called siderophores, that avidly bind iron and increase its bioavailability. K. pneumoniae variably produces four siderophores that antagonize host iron sequestration: enterobactin (Ent), glucosylated enterobactin (GEnt; also termed salmochelin), aerobactin (Abn), and yersiniabactin. Microbes synthesize and secrete siderophores, that bind and solubilize precipitated or otherwise unavailable iron in their microenvironments. Gram (−) bacterial TonB-dependent outer membrane receptors capture the resulting ferric siderophores to begin the uptake process. (Kumar “Siderophore-mediated iron acquisition by Klebsiella pneumoniae” Microbial Pathogenesis 9 April 2024)
Salmonella
Introduction:
There are more genomes available for Salmonella than any other bacterial genus. Over 575 000 Salmonella genomes are available in EnteroBase of which approximately 70 000 were Typhimurium.
Salmonella is a bacterial genus within the Family Enterobacteriaceae that consists of a large group of genetically similar organisms with the ability to infect a large number of animal hosts. The majority of clinical disease in animals and humans is caused by serovars within the Salmonella enterica subspecies and this can range from local gastroenteritis to a fatal disseminated disease. The exact clinical outcome of Salmonella infection depends largely on the individual serovar involved, the infected host species and the immunological status of the individual. See McSorley
Salmonella is a facultative anaerobe, rod-shapped, Gram-negative, flagellated bacterium that belongs to the enterobacteriacea family. The genus Salmonella has two species: Salmonella bongori and Salmonella enteria. Human outbreaks of salmonellosis are thought to be mostly caused by S. enterica. Salmonella cell walls are made up of proteins, lipoproteins, lipids and LPSs. The biological effects of bacteria are caused by endotoxins, which are found in LPSs and the lipid portion of the cell wall. Bacteria typically infiltrate the intestinal wall’s epithelial cells when they enter the digestive system through tainted food or water. Salmonella uses the type III secretion system, a multichannel protein that is encoded by SPI, to inject its effectors into the cytoplasm across the intestinal epithelial cell membrane. Bacterial effectors then rebuild the actin cytoskeleton of the host cell, causing the epithelial cell membrane to ripple or stretch outward in order to swallow the bacteria. The young old, pregnant and immunosuppressed are particularly vulnerable to infection from salmonellosis, with outbreaks stemming from a single food source showing that as little as 10-10 cells can cause the diase. Slmonella can be found in water for several days to several months, but it is also common and extremely persistent in dry settings. It has been desmontrated that pets can carry these germs around asymptomatically. As a result, when they periodically excrete these bacteria through their faeces, they can contaminate the environment and other animals that produce food. Traditional first line therapies for Salmonella infections include antibiotics such as chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. A multidrug resistant (MDR) strain of Salmonella is resistant to at lease 3 different classes of antibiotics. Fluoroquinolones and broad spectrum cephalosporins are the recommend antimicrobial medicines for the treatment of MDR S. typhi.
The prevalent intestinal illness salmonellosis, which is mostly caused by tainted meat and poultry, is thought to cost nations billions annually in losses in livestock. Human food born salmonellosis is a serious health issue in many nations. Treating salmonellosis can be expensive. Salmonella infections (Salmonellosis) continue to be one of the most common foodborne illnesses with significant global public ehalth impact. Worldwide there is an estimated 93.8 million cases and about 155,000 fatalities. Primarily, food producing animals such as pultry and their products, swine and cattle have been identified as important soruces of salmonellosis. Additionally, raw fruits and vegetables are among other food types.
Transmission: Humans are typically infected with Salmonella after consuming food or drinking water contaminated with bacteria and the transmission of most serovars uses the fecal-oral route
Pathogenesis: Following oral infection and survival in the acidic pH of the stomach, Salmonella has a good chance of colonizing the intestines. Expression of crucial virulence factors responsible for these events, such as flagella, fimbriae, and secretion systems, in the context of the host environment determines the potential success of the infection. Salmonella uses flagella to move along the host tissue surface before finding an appropriate binding site, fimbriae to attach to the cell surface, and invasion systems to actively enter host cells. The initial stages of Salmonella invasion are affected by a hostile host environment and trillions of microorganisms (microbiota) inhabiting the intestines. Most of the microbial species present in the microbiota are anaerobes, which decrease local oxygen levels and create a highly hypoxic environment within the intestines. Salmonella, as a facultative anaerobe, can benefit from both normoxic as well as hypoxic conditions. See Waszczuk
From the initial infection site in the PP, Salmonella can travel via the afferent lymphatics to the draining mesenteric lymph nodes (MLNs), and eventually gain access to the blood and systemic tissues via transit through efferent lymphatic vessels.
Innate Immune Response:
Salmonella initially interact with epithelial cells, which can recognize pathogenic bacteria and initiate an inflammatory response and recruit a variety of bone-marrow-derived phagocytes. The early immune response to Salmonella in PP and MLNs involves the recruitment of neutrophils and inflammatory monocytes, and these responses are important for delaying the spread of bacteria to systemic tissues.
In vitro studies showed that DCs located in the lamina propria under the gut epithelium of the small bowel extend processes across the tight junctions between the epithelial cells and capture bacteria from the luminal side of the gut. he major route of infection however, is via microfold cells or M cells. The specialized antigen-sampling M cells are located in the dome region of the Peyer’s Patches and are efficient in transportation of macromolecules and microorganisms to the underlying immune cell. After transcytosis by M cells, Salmonella reaches the subepithelial
dome of the Peyer’s patches and encounters an extensive network of resident macrophages, DCs and great numbers of B cells. nstead of being immediately destroyed by these cells,
Salmonella have evolved several mechanisms to survive in the harsh milieu of phagosomal compartments nd can be cytotoxic to macrophages by inducing apoptosis in vitro. See Ham
Adaptive Immune Response:
Recognition of Salmonella via the specific B cell receptor (BCR) on B cells results in internalization of Salmonella. Salmonella is able to survive intracellularly in primary B
cells in a non-replicative state. Following uptake of Salmonella, B cells do not go into apoptosis, but differentiate and start to produce Salmonella-specific antibodies. In addition, BCR-mediated
phagocytosis of Salmonella by B cells leads to antigen presentation via MHC class II and subsequent CD4+ T cell activation, which in turn boosts antibody production by the infected B cells. Salmonella-specific primary B cells that have internalized Salmonella also cross-present Salmonella antigens via MHC class I in a proteasome-dependent manner. Cross-presentation of Salmonella antigens by B cells reactivates Salmonella-specific CD8+ memory cells that acquire a cytotoxic phenotype and are efficient in killing of Salmonella-infected cells. Thus, antigen-specific B cells are an under appreciated type of cell for the induction of a cytotoxic T cell response against facultative intracellular bacteria. See Ham
Salmonella enterica: are lactose negative (unlike E coli which are lactose +. A large infectious dose is necessary. S. enterica is ubiquitous in animals. The source of most infections is from contaminated food products. Exposure to Salmonella bacteria can occur through food, drinking water, animal contact, environmental sources such as soil and water, and infected persons. More than 2400 S. enterica serovars have been identified to date and many of these serovars can infect both people and animals with disease. Most Salmonella enterica serovars are host-adaptied, which emans they can infect and cause sickness in a wide range of hosts. Animals that are asymptomatic but are considered “carriers” of Salmonella can develop clinical illness or subclinical infections.
Some Salmonella serotypes are highly host-specific. For example, S. enterica serovar Dublin is primarily associated with infections in cattle and sheep, whereas serovar Gallinarum is almost exclusively associated with infections in poultry. In contrast, other serotypes, such as serovars Enteritidis and Typhimurium, are associated with infection of a wider range of human and animal hosts. See Attribution of Salmonella enterica to Food Sources by Using Whole-Genome Sequencing Data
Nontyphoidal Salmonella infections place a large burden on public health; an estimated 79 million cases of foodborne nontyphoidal Salmonella infection occurred in 2010.
Most of the S. enterica serovars are motile and harbor flagella located at random points around the cell surface. The major structural protein that forms the flagella filaments is flagellin.
–enteric fever: Salmonella enterica serovar Paratyphi A is a human-specific serovar that, together with Salmonella enterica serovar Typhi and Salmonella enterica serovar Sendai, causes enteric fever.
Enteric fever is caused by Salmonella enterica serovars Paratyphi A, B, and C, which cause paratyphoid fever, and Typhi, which causes typhoid fever. Globally, an estimated 9.3 million cases and 107,459 deaths related to typhoid and paratyphoid fevers occurred in 2021; they especially affected children living in low- and middle-income countries. Preventing enteric fever by improving water, sanitation, and hygiene (WASH) infrastructure and practices remains challenging where resources are constrained, placing great reliance on antimicrobial therapy. Increasing multidrug resistance (MDR), defined as resistance to former first-line drugs including ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole (cotrimoxazole), in Salmonella Typhi is hampering successful therapy. However, previous studies show that MDR rates declined before the emergence of fluoroquinolone-nonsusceptible Salmonella Paratyphi A and Salmonella Typhi strains that render fluoroquinolone less suitable as first-line therapy prescribed by clinicians. Furthermore, the increase in azithromycin resistance in some settings is worrisom. See CDC
–Salmonella enterica serovar Infantis: presents an ever-increasing threat to public health because of its spread throughout many countries and association with high levels of antimicrobial resistance (AMR). Salmonella enterica subspecies enterica serovar Infantis is becoming an increasingly prevalent serovar globally. A 167% increase in human infections was observed in the United States during 2001–2016. Infantis is the predominant serovar isolated from broiler flocks and broiler meat, accounting for 56.7% of Salmonella isolates from broiler meat in 2018. Higher levels have been observed in Japan, at 72.2% of isolates from ground chicken, and levels of 84% were seen in broilers in Ecuador.
–Salmonella typhi are an obligate pathogen of humans (do not spread from species to species) and cause enteric (typhoid) fever. They may form a carrier state (typhoid Mary) and invade macrophages. The infectious dose is small (10) compared to S. enterica.
Typhoid fever is caused by infection with serovar Typhi or Paratyphi and is responsible for approximately 21.7 million cases and 217,000 deaths annually.
–Salmonella Typhimurium infection involve a series of coordinated events aimed at reaching, attaching to, and invading host cells. Virulence factors such as flagella, fimbriae, and secretion systems play crucial roles in these events and are regulated in response to the host environment.
S. Typhimurium is a rod-shaped, Gram-negative, facultative intracellular pathogen with a broad host range and an impressive metabolic versatility. The doubling time in a nutrient-rich medium at the optimal growth temperature of 37 °C is about 20min. S. Typhimurium is unable to ferment lactose. The ability to utilize citrate as a sole carbon source is not shared by the related S. Typhi serovar. The metabolic adaptability of S. Typhimurium is exemplified by the ability of the strain LT2 to grow on at least 100 different compounds as sole carbon or nitrogen sources. See Hinton
Protocols to enrich or select S. Typhimurium from a variety of sources, including faeces, are based on growth in the presence of agents such as selenite or tetrathionate which inhibit other bacterial species. Key biochemical properties include growth in selective media (brilliant green agar or xylose lysine deoxycholate) and fermentation of dextrose to produce H2 S gas in the triple sugar iron test.
The genome of S. Typhimurium ranges from 4.5 to 5Mb with a single circular chromosome and virulence plasmid, plus other plasmids. S. Typhimurium bacteria thrive in a wide variety of niches, including livestock, wild animals and the surface of plants. S. Typhimurium is mesophilic and can grow at a range of temperatures between 10 and 45 °C. The ability to survive and grow across a wide temperature range explains the persistence of the pathogen in remarkably diverse environments.
Salmonella is primarily transmitted to humans via the ingestion of contaminated food or through direct contact with infected individuals or animals. S. Typhimurium pathogenesis begins with adhesion to various surfaces on plants and in animals. The attachment of S. Typhimurium to mucosal surfaces in the mammalian intestine precedes invasion of epithelial cells and requires a range of adherent structures. In total, 12 adhesins have been discovered in S. Typhimurium, including chaperone-usher fimbriae, curli fimbriae, BapA and SiiE secreted by type 1 secretion systems, MisL, ShdA and SadA secreted by T5SS and potentially the PagN and Rck membrane proteins.
The flagellum of Salmonella enterica serovar Typhimurium is a supramolecular assembly consisting of at least three distinct functional parts: a basal body that acts as a bidirectional rotary motor together with multiple force generators, each of which serves as a transmembrane proton channel to couple the proton flow through the channel with torque generation; a filament that functions as a helical propeller that produces propulsion; and a hook that works as a universal joint that transmits the torque produced by the rotary motor to the helical propeller.
Efficient therapies include treatment with fluoroquinolones, trimethoprim-sulfamethoxazole (TMP-SMZ), ampicillin, or expanded-spectrum cephalosporins (e.g., ceftriaxone or cefixime). However, the increasing rates of antibiotic resistance among S. Typhimurium isolates have led to less use of TMP-SMZ and ampicillin, since resistance to these antimicrobial compounds is common. Even worse, resistance to multiple antimicrobial agents (multidrug resistance [MDR]) can be particularly high among S. Typhimurium isolates (>55%). See Vila
Shigella
Shigella is a causative agent of bacillary dysentery, which ultimately leads to severe bloody and mucous diarrhea (shigellosis). Most cases of shigellosis occur in developing countries and affect children under 5 years old. Although antibiotics are the standard care for shigellosis patients, antibiotic-resistant bacterium is becoming common. Therefore, it is urgently necessary to develop a safe and effective Shigella vaccine. Shigella have neither adherence factor nor flagella, but they are capable of efficiently invading the intestinal epithelium. Shigella injects a subset of effectors (secreted virulence proteins) via a type III secretion system (T3SS) (protein delivery system) into host cells, allowing the bacterium to invade, multiply within the intestinal epithelium, and subvert cellular and immune functions during bacterial internalization. See SasaKawa
Shigella is primarily a pediatric disease although infections in male homosexuals are also observed. Transmission is by the fecal-oral route. Because as few as 200 bacilli can establish disease, Shigella bacteria are responsible for shigellosis. shigellosis spreads rapidly in communities where sanitary standards are low. A shiga like toxin is produced by S. dysenteriae causing a bloody diarrhea much as with EHEC. Shigella invades M cells and replicates in the cytoplasm. It goes from cell to cell using the actin machinery of the infected cell. In the US, most Shigella is already resistant to antibiotics such as ampicillin and trimethoprim/sulfamethoxazole. Woldwide, resistance to Cipro is also on the rise.
Limmatech Biologics is currently evaluating the safety and immunogenicity of a Shigella vaccine candidate in a Phase I/II clinical trail in Kenyan children. The Sigella vaccine is tetravelent in that it incorporates four antigens. It covers up to 85 of diseases produced by Shigella.
Fhigella flexnerii: infection leads to shigellosis, an acute gastrointestina disease. Shigellosis affects socioeconomically disadvantaged and densely populated communiteis that have unsafe water, poor sanitation, and poor hygeine. (Dhabaan, “Detection of OXA-181 Carbapenemase in Sigella flexneri Emerging Infectious Diseases, 30(5), 2024).
Shigella sonnei: causes about 500k cases of diarhea in the US each year and is becoming increasingly resistant to antibiotics such as ciprofloxacin (Cipro). Cipro is often presecribed for travelers visiting other countries who develop diarhea while travelling. However, this may also be contributing to the bacterial resistance. Washing hands with soap and water, choosing hot foods and drinking only from sealed containers are protection measures.
Treatment:
The emergence of multidrug-resistant Shigella strains is a concerning trend. Multidrug-resistant strains resist multiple first line oral antimicrobials (i.e., ampicillin, trimethoprim/sulfamethoxazole, and ciprofloxacin). The situaiton is further complicated by enzyme-mediated beta-lactam resistance in Shigella bacteria, further impacting empiric therapy and making the isolates extensively drug resistant. Alhtough extesnively drug resistant isolates have remained susceptible to carbapenem therapy, carbapenem reistance in Shigells spp. thorugh imipenemase-type metallo-beta-lactamase, New Delhi metallo-beta-Lactamase, and Verona integron-encoded metallo-beta-lacamase has been reported. (Dhabaan, “Detection of OXA-181 Carbapenemase in Sigella flexneri Emerging Infectious Diseases, 30(5), 2024).
Immune Response:
–Autophagy is an essential cellular catabolic process, which targets proteins, organelles, and large protein aggregates by sequestering deleterious cargos within a double-membrane compartment, the autophagosome. Autophagy also plays a pivotal role as a part of the innate immune system, by acting as a cytosolic sensor to recognize DAMPs and PAMPs, and as an “executioner” that engulfs bacteria in autophagosomes that fuse with lysosomes, ultimately destroying bacteria within lysosomal compartments. Shigella prevents autophagic clearance by evading autophagic recognition.
Yersinia
Yersinia consists of several species. The Yersinia genus encompasses 2 enteropathogenic species, Y. enterocolitica and Y. pseudotuberculosis. Those bacteria are the cause of foodborne infections that range from mild enteritis, especially in children, to systemic infections in the elderly or patients with underlying disorders. See Genomic Characterization of Yersinia enterocolitica Isolates, Costa Rica
Y. pestis is the species that causes bubonic plague and was so devastating in the 14 century. This “black death” killed 25 million in Europe. It is transmitted via fleas and the reservoir is rodents, dogs and rabbits. It is a facultative intracellular bacterium and a zoonaotic
There are three clinical types of plague. 1) the first is bubonic (infected lymph nodes) which causes high fever and painful bubo (inflammatory swelling of lymph node). 2) The Second is pneumonic is the deadliest (almost 100% fatality rate) and transmissible by aerosol. 3) The third is septicemic (blood-born organisms).
Serratia:
This genus comprises gram-negative rods c . 0.9–2 μm long and 0.5–0.8 μm in diameter, and is part of the family Enterobacteriaceae . They consists of the following recognized species: Serratia entomophila , S. ficaria , S. fonticola , S. grimesii , S. liquefaciens , S. marcescens , S. odorifera , S. plymuthica , S. proteamaculans , S. quinivorans , S. rubidaea and S. ureilytica. Most Serratia spp. are motile by peritrichous flagella and are facultative anaerobic, chemoorganotrophic bacteria with both a respiratory and a fermentative type of metabolism. Being ubiquitous inhabitants of soil, water and plant surfaces, Serratia spp. are commonly associated with raw food materials and cause spoilage of various foods. In addition, they are capable of colonizing a wide variety of surfaces in the digestive tracts of rodents, insects, fish and humans
S. marcescens is implicated in a wide range of serious infections including pneumoni. S. marcescens infection has been attributed to many different sources. Outbreaks of infection have been traced to medical equipment including nebulisers. See Antimicrobes
Specific Types found in Non-humans
Edwardsiellosis, caused by Edwardsiella tarda, has been reported worldwide in economically important fish species, including Japanese eel (Anguilla japonica), red sea bream (Pagrus major), yellowtail (Seriola quinqueradiata), channel catfish (Ictalurus punctatus), and turbot (Scophthalmus maximus). Edwardsiella tarda is one of the serious fish pathogens, infecting both cultured and wild fish species. Research on edwardsiellosis has revealed that E. tarda has a broad host range and geographic distribution, and contains important virulence factors that enhance bacterial survival and pathogenesis in hosts. Although recent progress in edwardsiellosis research has enabled the development of numerous, highly effective vaccine candidates, these efforts have not been translated into a commercialized vaccine. see Park