Gram positive bacteria

Notifiable Diseases in the US (Wikipedia)

Gram positive bacteria are a diverse group. The most clinically important gram ositive pathogens include Staphylococcus, Streptococcus and Entercocci.

Gram-positive cocci

Enterococcus: Enterococcus refers to the genus name (singular) of Gram-positive, facultative anaerobic cocci commonly found in the gut, while Enterococci is the plural term used to describe multiple species or a group of bacteria within this genus. They are key causes of healthcare-associated infections, such as E. faecalis and E. faecium.

are gram positive cocci to elongated cocci in single or short chains. The are catalase negative, facultatively anaerobic. The Enterococci family can be found as part of the normal flora of the gastrointesitnal 30 tracts of humans and other animals. Over the last 30 years, Enterococci have become major nosocomial pathogens. They can cause infections at a variety of sites, including the urinary tract, bloodstream, endocardium, abdomen and biliary tract, as well as burn wounds and indwelling devices. Among the 15 species of Enterococci, E faecalis and E faecium are the most commonly associated with clinical infection.

Enterococci are the major Gram-positive cause of urinary tract infections (UTI). They can cause intra-abdominal and pelvic infections, bacteremia, which accounts for approximately 10% of bacteremia worldwide, and endocarditis.

Moreover, the constant increase of antibiotic resistance poses a serious therapeutic challenge, particularly for Enterococcus faecium. The emergence of isolates resistant to both vancomycin (VRE) and aminoglycosides raises questions about the use of this combination as a standard therapy and whether new therapy guidelines are necessary.

–Enterococcus faecalis: causes mostly nosocomial or opportunistic urinary tract infections, wound infections and bacteremia in seriously ill elderly pateints. Enterococci, a member of the human microbiome community, have gained notoriety over the past few decades as the leading nosocomial pathogens. They have been recognized as the second-most common cause of urinary tract infections and the third-most common cause of nosocomial bacteraemia.

One of the major reasons behind the ambiguous virulent phenotypes of E. faecalis strains could be the highly evolving nature of its Pathogenicity Island (PAI). Most of the virulence factors of E. faecalis are known to be harbored by an island of modular structure, where each module has probably been acquired through HGT events. See Dutta

–Enterococcus faecium: E. faecium has rapidly evolved as a worldwide nosocomial pathogen by successfully adapting to conditions in a nosocomial setting and acquiring resistance against glycopeptides. They have acquired a number of traits  making them successful in the hospital environment; such as an increase in antibiotic resistance genes and virulence genes enhancing biofilm formation and colonization.

E. faecalis has long been considered a predominantly extracellular pathogen; it adheres to and is taken up by a wide range of mammalian cells, albeit with less efficiencythan classical intracellular enteropathogens. Carbohydrate structures, rather than proteinaceous moieties, are likely to be primarily involved in the adhesion of E. faecalis to epithelial cells. Consistently, few adhesins have been implicated in the adhesion of E. faecalis to epithelial cells.

Micrococcus: are gram positive cocci in pairs, tetrads or clusters which are catalase positive, strictly aerobic and does not produce acid from glucose.

–Micrococcus luteus: is an opportunistic infection of immunocompromised patients.

Staphylococci (Staphylococcus): are  (so gram test can be used to identify) cocci which are most commonly found in clusters (another identification clue that distinguishes them from say Strept).

Because stophylococci are carried on the skin surface and in the nasopharynx, shedding of the bacteria is common and is responsible for many hospital acquired infections. They are sususpectable to disinfectants and antiseptic solutions but are capable of survival on dry surfaces for long periods. Transfer to a susceptible individual can be either by direct contact or by means of fomits (contaminated clothing or bed lines).

Treatment for staphylococcal infections include  (like cephalosporin) although plasmids encoding beta-lactamases are common.

The only species of Staphylococci which produces the enzyme coagulase is S. aureus whereas all other species are coagulase negative (a distinguishing characteristic).

–S. aureus: (see outline)

–S. epidermidis are circular, white, arranged in grape-like clusters, raised on sheep blood agar, coagulase negative (distinguish S. aureus above), non-hemolytic, catalase positive, facultative anaerobes. They are part of the human skin flora and can be found in mucous membranes. They are opportunisitc in that people with compromised immune systems are at risk for developing an infection.

–Staphylococcus lugdunensis is a species of coagulase-negative staphylococci that induces a variety of infectious diseases, including skin and soft tissue infection (SSTI), infective endocarditis (IE), and bone and PJI. In recent years, a growing body of evidence demonstrates the role of S. lugdunensis in a wide spectrum of diseases. Though the most common of these are skin and soft tissue infections (SSTIs). It has also been shown to infrequently cause bone, joint space, and prosthetic joint infections (PJIs); aggressive valvular endocarditis with significant mortality rates; urinary tract infections; and peritonitis.

Diagnosing a CNS such as S. lugdunensis begins with a clinical presentation suspicious for a staphylococcus infection, which is frequently expected to be a coagulase-positive staphylococcus infection (e.g., S. aureus).

Streptoccoci are and may occur in pairs or as chains. They are catalase negative (unlike Staphylococcus) and most species are  . 4 different schemes are used for classifying these organisms: 1) clinical presentation (pyogenic, oral, enteric);2) serological properties (Lancefield groupings); 3) hemolytic patterns (complete B hemolysis, incomplete alpha hemolysis, and no gamma-hemolysis) and 4. biochemical properties.

Group A streptococci are responsible for a wide variety of human diseases, the most common of which are nasopharyngitis and imeptigo. Nearly all clinical isolates have the antiphagocytic factor, M protein, on their surface. This virulence factor displays extreme antigenic diversity within its amino terminal region. It is these highly variable portions of M proteins which form the basis of the serological type which was formulated in the 1930s prior to knowledge of any structural detail. Group A streptococci can be divided into two major classes partly on the basis of their immunoreactivity with a pair of monoclonal antibodies directed to epitopes which lie within the relatively conserved half of M proteins. Class I isolates are defined as those binding one or both monoclonal antibodies, whereas class II isolates do not bind either monoclonal antibody. In addition, the classes differ in their ability to exhibit opacity factor activity, and in several pathogenic properties of these organisms (US 5,556,944).

–Streptococcus intermedius: is a Gram-positive bacteria that can cause brain and liver abscesses. It secretes a member of the cholesterol-dependent cytolysis (CDC) toxin family called Streptococcus intermedius intermedilysin (ILY). CDC play various roles in the pathogenesis of a wide variety of human and animal diseases caused by Gram positive bacterial. Human CD59 is a receptor for the cholesterol-dependent cytolysin intermedilysin (Giddings, Nature Structural & molecular biology, 2004).

–Streptococcus mitis: The mitis group of streptococci comprises species that are common colonizers of the naso-oral-pharyngeal tract of humans. Streptococcus pneumoniae and Streptococcus mitis are close relatives and share ∼60–80% of orthologous genes, but still present striking differences in pathogenic potential toward the human host. S. mitis has long been recognized as a reservoir of antibiotic resistance genes for S. pneumoniae, as well as a source for capsule polysaccharide variation, leading to resistance and vaccine escape. Both species share the ability to become naturally competent, and in this context, competence-associated killing mechanisms such as fratricide are thought to play an important role in interspecies gene exchange.

–Streptococcus pyogenes (S. pyogenes) (see outline)

 –Streptococcus agalactiae (Group B Streptococcus):

GBS is a beta-hemolytic encapsulated Gram-positive bacterium that colonizes the humangenitourinary and gastrointestinal tracts. Colonization is mediated by GBS surface proteinswhich allow effective adherence to the extracellular matrix on the epithelial surface15.Molecular pathogenesis of GBS is complex.

GBS produces numerous toxins (e.g., beta-haemolysin/cytolysin and CAMP factor) that proceed to cause direct cytotoxic tissue injury. GBS evades the host immune response via its polysaccharide surface capsule, which mimics human surface antigens and evades complement deposition, thus interfering with host opsonization and phagocytosis. Among bacteria undergoing phagocytosis, GBS is uniquely able to resist oxidative burst killing via expression of superoxide dismutase and production of carotenoid pigments that neutralize host oxidative stressors. 

GBS cause newborn meningitis and pneumonia. Colonies are larger than Group A, and beta hemolysis zone is smaller. They have an outermost capsule like Group A. They colonize the upper respiratory tract, lower GI tract, and vagina. Streptococcus agalactiae (Group B Streptococcus, GBS) is an important human pathogen that colonizes the urogenital and/or the lower gastro-intestinal tract of up to 40% of healthy women of reproductive age and is a leading cause of sepsis and meningitis in the neonates. GBS can also infect the elderly and immuno-compromised adults, and is responsible for mastitis in bovines. Like other Gram-positive bacteria, GBS can form biofilm-like three-dimensional structures that could enhance its ability to colonize and persist in the host. Biofilm formation by GBS has been investigated in vitro and appears tightly controlled by environmental conditions.See Mayo Clinic

Group B Streptococcus (GBS) emerged in the 1970s as a leading cause of neonatal sepsisin the United States, and currently accounts for approximately 30% of early-onset neonatalsepsis cases. The overall incidence of neonatal GBS disease has decreased over the last several decades, largely due to reductions in early-onset GBS disease in the era of protocolized screening for maternal GBS colonization and widespread use of GBS-targeted intrapartum antibiotic prophylaxis (IAP).

–Streptococcus pneumoniae (See outline)

–Viridan Streptococci are alpha and non-hemolytic streptococci. They are most often associated with dental caries.

Gram + Bacilli

Bacillus: Bacillus species are  which may form chains. They are spore formers and some have capsules. They require aerobic growth and can be grown on blood agar. The pathogenic ones secrete exotoxins.

Bacillus is a very diverse genus with more than 200 species, and the identification and diagnosis of potential disease-causing Bacillus species from patient material by the clinical lab can be challenging. This is especially the case for members of the B. cereus family. Despite their different species names, all these bacteria are often considered to be members of one species based on their high content of shared genes. See Cote

–B. anthracis (anthrax):

–B. cereus: are rod shaped, beta hemolytic, facultative anaerobes and can produce endospores. Bacillus cereus is an endospore-forming, gram-positive bacterium that commonly resides in the soil. Because of its location, Bacillus cereus is usually found on a variety of foods that come into close contact with contaminated soil, and can cause two different types of food borne illnesses: emetic and diarrheal. They are endemic and soil dwelling. Consequently, food products of plant origin frequently contain their spores. There is a marked seasonal variation in the spore content of raw milk, with higher levels during the pasture period, when the cows tetes may contain their spores from soil. Dirty teats that are not cleansed before milking are an important contamination source, particularly during wet weather. Some strains cause food poisoning which occurs due to survival of the bacterial endospores when food is improperly cooked. They can also cause opportunistic infections. After the ingestion of such contaminated foods, Bacillus cereus may incubate inside the infected organism for up to six hours before showing any symptoms that the emetic form displays like nausea, vomiting and abdominal cramps. Strains that produce the diarrheal form of the disease grow in a variety of foods ranging from vegetables to even meat products. Patients experience profuse diarrhea with abdominal pain and cramps…which begin around eight to sixteen hours after ingestion of the contaminated food. B. cereus illness is related to many foods – beef, turkey, rice, beans, vegetables. Specifically, the diarrheal illness is often related to meats, milk, vegetables, and fish. The emetic-type illness is most often associated with rice products, but it has also been associated with other types of starchy products such as potato, pasta, and cheese products. See Medic8.

Many strains of B. cereus are able to produce toxins and cause distinct types of food poisoning. Concerns over B. cereus contamination have increased because of the rapidly expanding number of chilled foods that may be pasteurized but may still contain viable spores. Spores from B. cereus can germinate and outgrow during storage, even at low temperatures. Major efforts to battle this increasing problem are focusing on determining the causes of the spore’s resistance and the mechanisms of germination. See Vries

While B. cereus is associated mainly with food poisoning, it is being increasingly reported to be a cause of serious and potentially fatal non-gastrointestinal-tract infections. The pathogenicity of B. cereus, whether intestinal or nonintestinal, is intimately associated with the production of tissue-destructive exoenzymes. Among these secreted toxins are four hemolysins, three distinct phospholipases, an emesis-inducing toxin, and proteases. The major hurdle in evaluating B. cereus when isolated from a clinical specimen is overcoming its stigma as an insignificant contaminant. Outside its notoriety in association with food poisoning and severe eye infections, this bacterium has been incriminated in a multitude of other clinical conditions such as anthrax-like progressive pneumonia, fulminant sepsis, and devastating central nervous system infections, particularly in immunosuppressed individuals, intravenous drug abusers, and neonates. See Botone

–B. clausii is a commonly used Bacillus spp. probiotic. Clinical data support its use for the treatment and prevention of gut barrier impairment. Small trials have investigated use in preterm neonates to prevent infection, treatment of nasal allergies and upper respiratory infections in children, and treatment of acute or chronic diarrhea, small-intestine bacterial overgrowth (SIBO), and adverse effects of Helicobacter pylori therapy in adults. See Drugs.com. Probiotic milk has been previously demonstrated to reduce the number of respiratory infections (RI) among children attending day care centres. See Marseglia

However caution should be exercised because Commensal/normal flora which are otherwise termed as ‘good bacteria’ are now causing infections in different group of patients, mostly immunocompromised individuals. Various host and environmental factors play a pivotal role in microbial transmigration from their normal habitat into the blood and other body sites. This has been reported for B. clausii. See Princess

–B. subtillis: is rod shaped, catalase positive, and can form a protective endospore. It is found in the soil and also considered as a normal human gut commensal. B.subtilis is non-pathogenic but can contaminate food and be considered an opportunistic pathogen among the immuno-compromised. They are used on seeds, vegetables, and plants as a fungicide because of their ability to produce antibiotics. B.subtilis inhabits the root system of the plant completing with disease causing organisms. Some B. subtilis strains are capable of producing toxins for insects. These strains are used by farms to protect their crops. See Microchem Laboratory

Clostridium (see outline)

Lactobacillus: are gram positive rods, sometimes in chains. They are catalase engative and have no endospores. They are isolated form a variety of foods (dairy, fish, grain, meat) and many are in normal flora (mouth, intestines, and vagina). There are no key pathogens in the clinial setting

Lysteria

–Listeria monocytogenes: is a ubiquitous, facultative intracellular, gram positive bacillus that causes listeriosis, an often fatal disease in newborns, pregnant women, and the immunocompromised. It is one of the most virulent food born pathogens. See CDC website

Listeria monocytogenes contamination affects various food commodities, including dairy products (e.g., cheeses, ice cream), ready-to-eat meats (e.g., deli meats), fruits, and vegetables. The ability to survive under adverse conditions enables L. monocytogenes to persist in food processing environments over extended periods. With the advent of high-throughput DNA sequencing, the Centers for Disease Control and Prevention (CDC) PulseNet and the US Food and Drug Administration GenomeTrackr programs started the routine use of whole-genome sequencing (WGS) as a subtyping tool in L. monocytogenes outbreak surveillance in September 2013. This tool has enabled public health agencies to connect cases over extended periods, refine case definitions, connect sporadic cases to sources, and link cases to common sources using WGS data from food and environmental isolates obtained through surveillance efforts. See CDC

Listeria monocytogenes is an etiologica gent for gastroenteritis but can also cause serius invasive disease. The incidence of invasive listeriosis is relatively low, but the case fatality rate is one of the highest among food borne infeftions. The severity of L. montyogenes infection, along with its ubiquitous environmental prsence and frequent outbreaks from commercially manufactured foods, results in major social and eoncomic impacts. (Andersson, “Effects of Decentralized Sequencing of National Listeria monocytogenes Genomic Surveillance, Australia, 2016-2023, Emerging Infectious Disease, 31(13), 2025)

The penicillin binding proteins (PBPs) of L. monocytogenes, involved in the construction of the bacterial cell wall, are the target of betalactam agents. Ampicillin inhibits preferentially the Listeria penicillin-binding proteins PBP1 and PBP2, has a good inhibitory activity against PBP3 and PBP4, and has lower affinity for PBP5. Ampicillin resistance is extremely infrequent in L. monocytogenes, probably involving less than 0.1% of the isolates. Tetracycline resistance is the most frequently acquired resistance phenotype in human isolates of L. monocytogenes. This phenotype is often due to ribosomal protection genes. Listeria monocytogenes contains plasmids in a high number of isolates, reaching > 80% of strains in some reports. However, plasmids containing antibiotic resistance genes are uncommon in the genus. See Coque

Mycobacteria:Mycobacterium is a dominant genus in the soil, and all its species are obligate aerobes. Oxygen availability is a major factor and evolutionary force determining the metabolic strategy of bacteria colonizing an environmental niche. In the soil, conditions can switch rapidly between oxia and anoxia, forcing soil bacteria to remodel their energy metabolism accordingly. Mycobacterium is a dominant genus in the soil, and all its species are obligate aerobes. Obligate aerobes require survival strategies to persist in temporarily oxygen-deprived environments. Mycobacterium is a dominant genus in the soil, and all its species are obligate aerobes. The obligate aerobe, for example, the soil actinomycete Mycobacterium smegmatis, adopts an anaerobe-type strategy by activating fermentative hydrogen production to adapt to hypoxia. See Cook

They are called “acid fast” in that they are very resistent to destaining after you stain them due to their complex cell wall lipids (mycolic acids). They are slow growing organisms and produce pigment depending on the presence or absence of light. Once inside a cell, mycobacteria are resistent to phagoccytosis. Some important types of mycobacteria are the following:

–Mycobacterium tuberculosis: See outline

–M. leprae: occurs mostly in the tropics. Diagnosis is by way of a skin test reagent (lepromin), extracted from autoclaved tissue harvested from patients with leprosy. Therapy is with dapsone which has to be administered for years.

–M. avium is rare in immunocompetent people but a common opportunistic bacterial infection in patients. M. avium complex (MAC) is the most common cause for both disseminated Mycobacterium disease and death in patients with AIDS in the developed world (~25%-50% of adults and 10% of children with AIDS are infected).

–M. kansasii is a pulmonary infection, resembling TB. It has a photoinducible pigment.

–M. marinum are acquired by contact with contaminated fresh water or salt water. For this reason, they are called “swimming pool granulomas.” It responds well to antibiotics.

–M. fortuitum are most commonly associated with disease following the introduction of the bacteria into deep subcutaneous tissues by trauma or intravenous catheter, contaminated wound dressing, etc. Infections with these organisms are increasing as more invasive procedures are performed on hospitalized patients. These organisms are faster growing than other mycobacteria.

–Mycobacterium smegmatis can rapidly switch between fermentative hydrogen production and hydrogen oxidation coupled to either oxygen or fumarate reduction depending on electron acceptor availability. Mycobacterium smegmatis can switch between fermentation, anaerobic respiration, and aerobic respiration. See cook

Gram Positive Bacteria that Infects Non-Humans

Paenibacillus larvae is a Gram-positive, spore-forming bacterium that is the causative agent of American foul brood (AFB), the most devastating bacterial disease of the honeybee. P. larvae is antibiotic resistant, complicating treatment efforts. Bacteriophages that target P. larvae are rapidly emerging as a promising treatment. See Genon