Chapter 23 : Bacterial Persistence: Strategies for Survival

Contrasting epidemic dynamics of measles and TB. (A) Numerical simulation of a measles epidemic initiated by entering one infectious case at time zero into a susceptible population of 500,000. The simulation illustrates successive epidemic waves at roughly 6- to 12-month intervals. Redrawn from Keeling (1997) with permission of the American Association for the Advancement of Science. (B) Numerical simulation of a tuberculosis epidemic initiated by entering one infectious case at time zero into a population of 200,000. The simulation illustrates the relative contribution of three types of disease to the overall incidence: fast (progressive primary), slow (postprimary), and relapse tuberculosis. A fourth type, exogenous reinfection, is not included in the model but would presumably increase the peak level and duration of the epidemic. Redrawn from Blower et al. (1995) with permission of the publisher. The contrasting epidemic dynamics of measles and tuberculosis are also reflected in the CCS required for endemicity, which is roughly 250,000 for measles ( Keeling, 1997 ) and 500 or less for tuberculosis ( McGrath, 1988 ).

T. pallidum spirochetes visible as long, slender, spiral threads in a dermal syphilis lesion. Warthin-Starry stain. Magnification, ×695. Reprinted from Smith et al. (2000) with permission of the publisher.

Stages of the multistage disease syphilis. (A) Primary syphilis. Chancre of the palm. The primary chancre most often occurs on the genitalia, but extragenital chancres are not rare. Without treatment, the chancre usually heals in 1 to 4 weeks. (B) Secondary syphilis. Generalized papulosquamous lesions. (C) Tertiary syphilis. Gummas of the leg. Ulcerative gummas can occur in multiple organ systems. The onset is usually 5 to 20 years after the primary stage. (D) Gumma of tertiary syphilis. A central region of caseation necrosis is surrounded by an epithelioid granulomatous reaction (including multinucleated giant cells) and peripheral fibrosis. H&E stain. Magnification, ×126. Panels A to C reprinted from Sauer and Hall (1996) with permission of the publisher; panel D reprinted from Smith et al. (2000) with permission of the publisher.

Relapsing fever. Spikes of fever are accompanied by waves of spirochetemia. In each successive wave, a new antigenic variant dominates (indicated by different shapes). As the bacteria are cleared by the specific humoral response, the fever subsides. However, expansion of a newly emergent variant brings about another febrile episode within a few days. Reviewed by Barbour (1990) .

Antigenic and phase variation of pili in N. gonorrhoeae. (A) Antigenic variation. Pilin is encoded by one or two pilE expression loci. Variant pilin sequences are stored in silent pilS cassettes, which lack the 5′ coding and promoter sequences required for expression. Nonreciprocal recombination between pilS and pilE sequences gives rise to expression of variant pilin subunits. Modular recombination can generate mosaic pilE loci containing sequences derived from several distinct pilS loci. (B) Phase variation. PilC is a minor subunit that is required for proper assembly and export of pili. A run of G residues near the 5′ end of the pilC gene can vary in length due to slipped-strand DNA synthesis during chromosome replication. Depending on the exact number of G residues, the downstream pilC coding sequences may be in or out of frame for translation.

Chest X-ray of a 70-year-old woman shortly before her death. “A white woman had cavitary tuberculosis of 41 years' duration. She had bilateral bronchiectasis, cavitation of the right upper lobe, a collapsed left lung, pleural effusion, and an induced left pneumothorax of 36 years' duration. She had received no antituberculous drugs for 28 years from the onset of her illness, and these drugs, when finally prescribed, were taken inadequately. Pleural effusion present for 28 years required aspiration. Mycobacterium tuberculosis recovered by culture of sputum was resistant to all antituberculous drugs except streptomycin (which the patient had never received due to allergy).” Reprinted from Edwards et al. (1970) , with permission of the American Lung Association.

The treated pulmonary lesion and its tubercle bacillus: death and resurrection. Resected lung lesions from patients on chemotherapy were cultured. “Open” and active cavitary lesions, with patent connections to the airways, yielded drugresistant tubercle bacilli in the normal time frame (less than 2 months of incubation). “Closed” and dormant encapsulated lesions, with no apparent connections to an airway, yielded drug-sensitive tubercle bacilli only after extended incubation (3 to 10 months). Derived from Vandiviere et al. (1956) .

Biofilm biogenesis. Planktonic bacteria swim to a surface via flagellar motility and attach (mediated by flagella and nutrient sensing mechanisms). Replication on the surface leads to the formation of a monolayer of cells, which aggregate by twitching motility (mediated by type IV pili) and adhere to each other, forming surface-attached microcolonies. These microcolonies become embedded within a thick layer of secreted EPS. As the cell density increases, quorum sensing via HSLs synthesized by LasI triggers the developmental changes required for formation of the correct architecture and thickness of the fully mature biofilm. The mature biofilm is penetrated by fluid-filled channels that deliver nutrients and remove wastes. Bacteria within the biofilm are protected from destruction by antibodies, phagocytes, and antimicrobials. The steps leading to dissociation of biofilms and reversion to the planktonic form are poorly understood but may involve environmental sensing and programmed disruption or simple physical forces such as shear stress from fluid flow. Redrawn from Costerton et al. (1999) with permission of the American Association for the Advancement of Science.