title: Legless pathogens: how bacterial physiology provides the key to understanding pathogenicity.
abstract: This review argues that knowledge of microbial physiology and metabolism is a prerequisite to understanding mechanisms of pathogenicity. The ability of Neisseria gonorrhoeae to cope with stresses such as those found during infection requires a sialyltransferase to sialylate its lipopolysaccharide using host-derived CMP-NANA in the human bloodstream, the ability to oxidize lactate that is abundant in the human body, outer-membrane lipoproteins that provide the first line of protection against oxidative and nitrosative stress, regulation of NO reduction independently from the nitrite reductase that forms NO, an extra haem group on the C-terminal extension of a cytochrome oxidase subunit, and a respiratory capacity far in excess of metabolic requirements. These properties are all normal components of neisserial physiology; they would all fail rigid definitions of a pathogenicity determinant. In anaerobic cultures of enteric bacteria, duplicate pathways for nitrate reduction to ammonia provide a selective advantage when nitrate is either abundant or scarce. Selection of these alternative pathways is in part regulated by two parallel two-component regulatory systems. NarX-NarL primarily ensures that nitrate is reduced in preference to thermodynamically less favourable terminal electron acceptors, but NarQ-NarP facilitates reduction of limited quantities of nitrate or other, less favourable, terminal electron acceptors in preference to fermentative growth. How enteric bacteria repair damage caused by nitrosative and oxidative damage inflicted by host defences is less well understood. In both N. gonorrhoeae and Escherichia coli, parallel pathways that duplicate particular biochemical functions are far from redundant, but fulfil specific physiological roles.
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cole
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D009344:Neisseria gonorrhoeae / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins