Gram Positive Bacilli: Non-Spore Forming

Morphology. Gram positive rods, club-shaped and pleomorphic, characteristically arranged at angles to one another resembling Chinese letters or a picket fence. Metachromatic granules, Babes-Ernst granules, are visible with special stains, such as Albert stain, representing stored phosphate reserves.

Important toxins. Diphtheria toxin is a classic A-B exotoxin, encoded not by the bacterial chromosome itself but by a lysogenic bacteriophage. Only strains carrying this phage, termed toxigenic strains, produce toxin and cause the severe systemic disease; nontoxigenic strains cause only local, typically milder disease.

The B subunit binds a host cell receptor and mediates entry; the A subunit ADP-ribosylates and thereby inactivates elongation factor 2, halting host cell protein synthesis, causing local tissue necrosis and, once absorbed systemically, distant organ toxicity, myocarditis, peripheral neuropathy.

Transmission. Respiratory droplets and direct contact with respiratory secretions or skin lesions. Humans are the only reservoir.

Disease syndromes. Respiratory diphtheria presents as pharyngitis progressing to formation of a thick, grey, adherent pseudomembrane over the tonsils and pharynx, which bleeds if forcibly removed, a distinguishing clinical feature from other causes of exudative pharyngitis, with risk of airway obstruction from membrane extension, plus systemic toxin-mediated complications including myocarditis, the leading cause of death, and demyelinating peripheral neuropathy, typically delayed in onset, following initial recovery from the acute illness.

Cutaneous diphtheria is a chronic, nonhealing skin ulcer, typically with less systemic toxicity than respiratory disease, but still capable of causing systemic complications and, importantly, serving as a reservoir for onward transmission.

Diagnosis. Culture on selective and differential media, tellurite agar, on which the organism produces characteristic black colonies, from a swab taken beneath the pseudomembrane. Toxin production is confirmed separately, historically the Elek test, an immunoprecipitation assay, increasingly PCR-based toxin gene detection, since organism identification alone does not establish toxigenicity, and treatment decisions, specifically the use of diphtheria antitoxin, depend on this distinction.

Key microbiological features. The toxoid form of diphtheria toxin is a core component of routine childhood immunisation, part of combined DTaP and Tdap-type vaccines. Treatment of confirmed or strongly suspected toxigenic disease requires prompt antitoxin administration, to neutralise circulating, not yet cell-bound, toxin, in addition to antibiotics, which control the organism but do not neutralise toxin already produced.

Morphology. Gram positive rods, small, arranged singly or in short chains, characteristically motile at room temperature, 25 degrees Celsius, giving a distinctive tumbling motility on wet preparation, but nonmotile or weakly motile at body temperature, 37 degrees Celsius, an unusual and diagnostically useful temperature-dependent property.

Important toxins and virulence mechanisms. Listeriolysin O is a pore-forming toxin that allows the organism to escape the phagosome after phagocytic uptake and enter the host cell cytoplasm. The organism then exploits host cell actin polymerisation, via the bacterial surface protein ActA, to propel itself directly from cell to cell, avoiding extracellular exposure to antibody and complement entirely.

This intracellular, cell-to-cell spread mechanism is the organism's defining virulence strategy and the reason cell-mediated, T cell, immunity, rather than antibody-mediated immunity, is the principal host defence, explaining why Listeria disproportionately affects patients with impaired cell-mediated immunity.

Transmission. Foodborne, classically associated with unpasteurised dairy products, soft cheeses, deli meats, and pre-prepared refrigerated foods. The organism's ability to grow, albeit slowly, at refrigeration temperatures is a key food safety concern, distinguishing it from most other foodborne bacterial pathogens, which are inhibited by cold storage.

Disease syndromes. In healthy adults, infection is often mild or asymptomatic gastroenteritis. The organism's major clinical significance lies in its disproportionate severity in specific high-risk groups given the cell-mediated immunity dependence above.

Pregnant women show increased susceptibility due to relative pregnancy-associated immune modulation; maternal infection is often mild but can cause transplacental fetal infection, leading to miscarriage, stillbirth, preterm labour, or neonatal sepsis, granulomatosis infantiseptica in severe cases. Neonates are affected by early-onset disease, acquired transplacentally or during delivery, and late-onset disease.

The elderly and immunocompromised patients, including those on immunosuppressive therapy and, notably, those with impaired cell-mediated immunity from any cause, are at markedly increased risk of bacteraemia and meningitis or meningoencephalitis, with Listeria being a classic cause of meningitis specifically in these high-risk age or immune groups, neonates, elderly, immunocompromised, rather than in previously healthy young adults.

Diagnosis. Blood or CSF culture. Growth may be slow, and cold enrichment, prolonged incubation of the specimen at refrigeration temperature, exploiting the organism's unusual cold tolerance to selectively allow it to outgrow other flora, can be used to enhance recovery from mixed or low-inoculum specimens in specialised settings. The tumbling motility at room versus body temperature is a classic confirmatory laboratory clue.

Key microbiological features. Intrinsic resistance to cephalosporins, all generations, is a clinically critical point: standard empirical meningitis regimens using a third-generation cephalosporin do not cover Listeria, so ampicillin must be specifically added to empirical therapy whenever a patient's age or immune status places them in a Listeria-risk group.