The factors that enhance the transmission of pathogens during epidemic spread are ill defined. Water-borne spread of the diarrhoeal disease cholera occurs rapidly in nature, whereas infection of human volunteers with bacteria grown in vitro is difficult in the absence of stomach acid buffering. It is unclear, however, whether stomach acidity is a principal factor contributing to epidemic spread. Here we report that characterization of Vibrio cholerae from human stools supports a model whereby human colonization creates a hyperinfectious bacterial state that is maintained after dissemination and that may contribute to epidemic spread of cholera. Transcriptional profiling of V. cholerae from stool samples revealed a unique physiological and behavioural state characterized by high expression levels of genes required for nutrient acquisition and motility, and low expression levels of genes required for bacterial chemotaxis.

Colonization by the gastric pathogen Helicobacter pylori has been shown to be intricately linked to the development of gastritis, ulcers, and gastric malignancy. Little is known about mechanisms employed by the bacterium that help it adapt to the hostile environment of the human stomach. In an effort to extend our knowledge of these mechanisms, we utilized spotted-DNA microarrays to characterize the response of H. pylori to low pH. Expression of approximately 7% of the bacterial genome was reproducibly altered by shift to low pH. Analysis of the differentially expressed genes led to the discovery that acid exposure leads to profound changes in motility of H. pylori, as a larger percentage of acid-exposed bacterial cells displayed motility and moved at significantly higher speeds. In contrast to previous publications, we found that expression of the bacterial virulence gene cagA was strongly repressed by acid exposure. Furthermore, this transcriptional repression was reflected at the level of protein accumulation in the H. pylori cell.

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Vibrio cholerae is a facultative pathogen of humans that must survive exposure to inorganic and organic acids in the stomach and small intestine. To learn more about the mechanisms by which this pathogen colonizes the intestinal tract, we used a recombinase gene fusion reporter to identify transcripts induced during infection in an adult rabbit model of cholera. One of the genes identified was cadA, which encodes an inducible lysine decarboxylase. CadA was also induced during infections of the suckling and adult mouse intestines, and in vitro under conditions of low pH and high lysine concentration. We show that V. cholerae is capable of mounting an acid tolerance response (ATR) to both inorganic and organic acid challenges. Mutational analyses revealed a significant role for cadA, but not for speF, which encodes an ornithine decarboxylase, in both inorganic and organic ATR. Potential roles for toxR, toxT and rpoS in ATR were examined, and it was found that toxR plays a ToxT‐independent role in mediating organic ATR, whereas rpoS played no detectable role in either ATR. Transcriptional analysis showed that the toxR defect in ATR is not caused by decreased cadA transcription. Despite induction of cadA in these animal models, competition assays revealed that neither cadA nor speF alone or together were required for colonization of suckling or adult mice. However, acid‐adapted wild‐type V. cholerae exhibited a major competitive advantage over unadapted cells during colonization of suckling mice.

Helicobacter pylori persistently colonizes the stomach of the majority of the world's population and is a tremendous medical burden due to its causal role in diverse gastric maladies. Since the stomach is a constantly changing environment, successful colonization of H. pylori within this niche requires regulation of bacterial gene expression to cope with the environmental fluctuations. In H. pylori, the ferric uptake regulator (Fur) has been shown to play an intricate role in adaptation of the bacterium to two conditions known to oscillate within the gastric mucosa: iron limitation and low pH. To extend our knowledge of the process of regulation and adaptation in H. pylori, we show that Fur is required for efficient colonization of the Mongolian gerbil: the mutant strain exhibits a 100-fold increase in the 50% infectious dose, as well as a 100-fold defect in competitive colonization, when coinfected with wild-type bacteria. Furthermore, we used DNA microarrays to identify genes whose expression was altered in a Fur-deficient strain. We show that the Fur regulon of H. pylori consists of approximately 30 genes, most of which have been previously annotated as acid stress associated. Finally, we investigate the role of Fur in acid-responsive modulation of gene expression and show that a large number of genes are aberrantly expressed in the Fur mutant specifically upon acid exposure. This fact likely explains the requirement for this regulator for growth and colonization in the stomach.