Bacterial persistence and expression of disease

Abstract

A considerable body of experimental and clinical evidence supports the concept that difficult-to-culture and dormant bacteria are involved in latency of infection and that these persistent bacteria may be pathogenic. This review includes details on the diverse forms and functions of individual bacteria and attempts to make this information relevant to the care of patients. A series of experimental studies involving host-bacterium interactions illustrates the probability that most bacteria exposed to a deleterious host environment can assume a form quite different from that of a free-living bacterium. A hypothesis is offered for a kind of reproductive cycle of morphologically aberrant bacteria as a means to relate their diverse tissue forms to each other. Data on the basic biology of persistent bacteria are correlated with expression of disease and particularly the mechanisms of both latency and chronicity that typify certain infections. For example, in certain streptococcal and nocardial infections, it has been clearly established that wall-defective forms can be induced in a suitable host. These organisms can survive and persist in a latent state within the host, and they can cause pathologic responses compatible with disease. A series of cases illustrating idiopathic conditions in which cryptic bacteria have been implicated in the expression of disease is presented. These conditions include nephritis, rheumatic fever, aphthous stomatitis, idiopathic hematuria, Crohn's disease, and mycobacterial infections. By utilizing PCR, previously nonculturable bacilli have been identified in patients with Whipple's disease and bacillary angiomatosis. Koch's postulates may have to be redefined in terms of molecular data when dormant and nonculturable bacteria are implicated as causative agents of mysterious diseases.

Cell-wall deficient L. monocytogenes L-forms feature abrogated pathogenicity

“…Interestingly, persistence in macrophages has also been reported for S. aureus L-forms. After intra-phagosomal formation of S. aureus L-forms in alveolar macrophages of rats, the phagocytes were incapable of lysosomal acid-phosphatase activation and phagosome-lysosome fusion (Michailova et al, 2007), which could suggest that these L-forms may represent persisters (Beaman and Scates, 1981; Domingue and Woody, 1997). Consequently, the wall-less state of bacteria had been speculated to possibly assume roles in chronic disease, based on the lack of immune recognition (Domingue and Woody, 1997; Domingue, 2010).…”

Inflammation and vitamin D: the infection connection

“…The inability of most research labs to culture cell wall deficient (CWD) bacteria has been an obstacle to their acceptance, and reliance on Koch’s postulates has made it difficult to correlate CWD bacteria to specific diseases [72]. But some researchers believe Koch’s postulates may have to be redefined in terms of molecular data when dormant and non-culturable bacteria are implicated as causative agents of mysterious diseases [73]. O´Connor et al [74] (in their article entitled Emerging Infectious Determinants of Chronic Diseases) report, “microbes can now be irrefutably linked to pathology without meeting Koch’s postulates” and “…powerful tools of molecular biology have exposed new causal links by detecting difficult-to-culture and novel agents in chronic illness settings.”…”

“…Many microbiologists now believe at least some, if not all, of the inflammation which drives the chronic disease process is caused by the presence of these stealthy intracellular pathogens [86]. A considerable body of experimental and clinical evidence supports the concept that difficult-to-culture and dormant bacteria are involved in latency of infection and that these persistent bacteria may be pathogenic [73, 87, 88]. McDougal [89] states, “Evidence now confirms that non-communicable chronic diseases can stem from infectious agents.”…”

Predicted highly expressed genes in Nocardia farcinica and the implication for its primary metabolism and nocardial virulence

“…The mechanisms of Nocardia pathogenesis are complex and not fully understood (Domingue and Woody 1997). In N. asteroides, the studies showed relative virulence correlated with many factors, such as the abilities to inhibit phagosome-lysosome fusion in phagocytes; to neutralize phagosomal acidification; to detoxify the microbicidal products of oxidative metabolism; to modify phagocyte function; to grow within phagocytic cells; and to attach to, penetrate, and grow within host cells (Beaman and Beaman 1994).…”