SummaryThe flagellar system of Helicobacter pylori , which comprises more than 40 mostly unclustered genes, is essential for colonization of the human stomach mucosa. In order to elucidate the complex transcriptional circuitry of flagellar biosynthesis in H. pylori and its link to other cell functions, mutants in regulatory genes governing flagellar biosynthesis ( rpoN , flgR , flhA , flhF , HP0244) and whole-genome microarray technology were used in this study. The regulon controlled by RpoN, its activator FlgR (FleR) and the cognate histidine kinase HP0244 (FleS) was characterized on a genome-wide scale for the first time.
Functional characterization of the antagonistic flagellar late regulators FliA and FlgM of Helicobacter pylori and their effects on the H. pylori transcriptome of sigma and anti-sigma factors, but the genes controlled by these differ markedly from the Salmonella/Escherichia coli paradigm.
IntroductionHelicobacter pylori persistently colonizes the stomach of one half of the world population. It is one of the most common human pathogens, causing chronic gastritis in all infected persons and, in some individuals, causes more severe diseases including ulcers and gastric cancer. The only known habitat of H. pylori is the gastric mucosa of humans. Helicobacter pylori requires flagelladependent motility to survive and multiply in this particular ecological niche (Eaton et al., 1996;Mankoski et al., 1999). Some components of the flagellar apparatus of H. pylori have been studied intensely over the last two decades. Many different flagellar components have been identified, including two flagellins that are governed by s 28 and s 54 promoters respectively O´Toole et al., 1994;Foynes et al., 1999;Kim et al., 1999;Spohn and Scarlato, 1999). The publication of H. pylori genome sequences has facilitated the identification of additional proteins with putative functions in motility, based on their similarity to known motility proteins of Salmonella typhimurium, Bacillus subtilis and other well characterized bacteria (Tomb et al., 1997;Alm et al., 1999). Reconstruction of the H. pylori motility system, based on the original annotations of the two published genome sequences, showed several differences between H. pylori and the Enterobacteriaceae. One of the most notable differences between the enterobacterial motility regulation cascade and the H. pylori system was the apparent lack of two key regulatory components, the flhCD master operon, and the antisigma (s 28 ) factor gene flgM. This is consistent with a general scarcity of regulatory proteins in H. pylori. The flagellar regulatory system of S. typhimurium is an intricate network of temporally regulated genes, which are organized into a transcriptional hierarchy (Macnab, 1996;Aizawa, 2000;Chilcott, 2000). At the top of the hierarchy are the flagellar master regulators FlhCD (class 1), which act as positive transcriptional regulators on the class 2 promoters. Class 2 operons encode
The gastric pathogen Helicobacter pylori shows tremendous genetic variability within human populations, both in gene content and at the sequence level. We investigated how this variability arises by comparing the genome content of 21 closely related pairs of isolates taken from the same patient at different time points. The comparisons were performed by hybridization with whole-genome DNA microarrays. All loci where microarrays indicated a genomic change were sequenced to confirm the events. The number of genomic changes was compared to the number of homologous replacement events without loss or gain of genes that we had previously determined by multilocus sequence analysis and mathematical modeling based on the sequence data. Our analysis showed that the great majority of genetic changes were due to homologous recombination, with 1/650 events leading to a net gain or loss of genes. These results suggest that adaptation of H. pylori to the host individual may principally occur through sequence changes rather than loss or gain of genes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.