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Helicobacter pylori's Helical Shape Promotes Gastric Colonization
Gastroenterology and Hepatology News Richard Peek and K. Rajender Reddy, Section Editors
Mucosal Adherent Bacteria and Colorectal Adenomas
T
he relationship between commensal intestinal bacteria and colorectal adenomas is unclear because the human bowel is colonized by complex and diverse bacterial communities. However, recent findings from the University of North Carolina at Chapel Hill School of Medicine and published in the journal Gut Microbes suggest that alterations in bacterial community composition associated with adenomas may contribute to colorectal cancer etiology. The study led by Temitope O. Keku, PhD, Research Associate Professor of Medicine, UNC Center for Gastrointestinal Biology and Disease, evaluated adherent bacteria in normal colonic mucosa isolated from 21 adenoma and 23 nonadenoma subjects. Terminal restriction fragment length polymorphism, clone se-
quencing and fluorescent in situ hybridization analysis of the 16S rRNA genes were among the molecular methods used to characterize adherent bacteria. In all, 335 clones were sequenced and processed. The most dominant phyla were Firmicutes (62%), Bacteroidetes (26%), and Proteobacteria (11%). “We observed significantly higher abundance of Proteobacteria (P ⬍ .05) and lower abundance of Bacteroidetes (P ⬍ .05) in cases compared to controls,” the authors state. “Cases had higher bacterial diversity and richness than controls.” In particular, Proteobacteria was in higher abundance in cases than in controls. It is still not clear whether alterations in bacterial composition cause adenomas, or, conversely, if adenomas cause this altered balance. Keku plans to conduct more studies, including testing whether certain groups of bacteria promote cancer growth in
Helicobacter pylori’s Helical Shape Promotes Gastric Colonization
N
ew research has determined for the first time that, at least when it comes to Helicobacter pylori’s (Figure 1) ability to colonize the stomach, shape matters. In a study reported in the May 28 issue of Cell, microbiologist Nina Salama, PhD, and colleagues at the Fred Hutchinson Cancer Research Center and the University of Washington in Seattle discovered a family of LytM peptidase homologs—3 peptidases and a scaffolding protein— that collaborate in generating the bacterium’s helical shape. Using a mouse model, the researchers found that laboratory-engineered mutant strains of H pylori that were deficient in these cell wall proteins fail to twist properly and, consequently, are unable to colonize the gastric mucosa.
Figure 1. Helicobacter pylori
The study further determined that the helical shape of H pylori requires relaxation of peptidoglycan cross-linking. “The crosslinks preserve the structural integrity of the bacterial wall, but if certain links are cleaved or relaxed by
animal models. The researcher is expanding the study to analyze samples from 600 patients using next-generation sequencing technology “to provide deeper coverage of bacterial communities.” The ultimate goal may be to determine if the differences in bacterial populations found in the mucosa lining the colon also exist within the luminal fraction. If so, it could mean less invasive screening for cancer and more cancers being caught earlier, when survival rates are higher. “Our findings suggest that adherent bacteria may be significant players in the development of adenomas and colorectal cancer,” the authors state. “Extension of these findings could lead to strategies to manipulate the microbiota to prevent colorectal adenomas and cancer as well as to identify individuals at high risk.” See: Shen, et al, Gut Microbes, May/ June 2010.
these proteins, it allows the rod shape to twist into a helix,” Salama said. Other disease-inducing bacteria that harbor these proteins include Vibrio cholera and Campylobacter jejuni. Thus, it seems that unlocking the keys to H pylori’s helical structure may lead to better antibiotic drugs for diseases ranging from ulcers and stomach cancer to diarrhea and cholera. “In this work, we have established H pylori as an excellent model to elucidate molecular determinants of helical cell shape in the Proteobacteria and the selective role of shape during host colonization,” the authors state. “Our discovery of a family of LytM peptidase homologs required for efficient stomach colonization by H pylori suggests new targets for antimicrobial therapy that may have efficacy in other pathogens that utilize these proteins, including Vibrio and Campylobacter species.” See: http://www.cell.com/ fulltext/S0092-8674(10)00365-X. GASTROENTEROLOGY 2010;139:367–368
Mucosal Adherent Bacteria and Colorectal Adenomas
T
he relationship between commensal intestinal bacteria and colorectal adenomas is unclear because the human bowel is colonized by complex and diverse bacterial communities. However, recent findings from the University of North Carolina at Chapel Hill School of Medicine and published in the journal Gut Microbes suggest that alterations in bacterial community composition associated with adenomas may contribute to colorectal cancer etiology. The study led by Temitope O. Keku, PhD, Research Associate Professor of Medicine, UNC Center for Gastrointestinal Biology and Disease, evaluated adherent bacteria in normal colonic mucosa isolated from 21 adenoma and 23 nonadenoma subjects. Terminal restriction fragment length polymorphism, clone se-
quencing and fluorescent in situ hybridization analysis of the 16S rRNA genes were among the molecular methods used to characterize adherent bacteria. In all, 335 clones were sequenced and processed. The most dominant phyla were Firmicutes (62%), Bacteroidetes (26%), and Proteobacteria (11%). “We observed significantly higher abundance of Proteobacteria (P ⬍ .05) and lower abundance of Bacteroidetes (P ⬍ .05) in cases compared to controls,” the authors state. “Cases had higher bacterial diversity and richness than controls.” In particular, Proteobacteria was in higher abundance in cases than in controls. It is still not clear whether alterations in bacterial composition cause adenomas, or, conversely, if adenomas cause this altered balance. Keku plans to conduct more studies, including testing whether certain groups of bacteria promote cancer growth in
Helicobacter pylori’s Helical Shape Promotes Gastric Colonization
N
ew research has determined for the first time that, at least when it comes to Helicobacter pylori’s (Figure 1) ability to colonize the stomach, shape matters. In a study reported in the May 28 issue of Cell, microbiologist Nina Salama, PhD, and colleagues at the Fred Hutchinson Cancer Research Center and the University of Washington in Seattle discovered a family of LytM peptidase homologs—3 peptidases and a scaffolding protein— that collaborate in generating the bacterium’s helical shape. Using a mouse model, the researchers found that laboratory-engineered mutant strains of H pylori that were deficient in these cell wall proteins fail to twist properly and, consequently, are unable to colonize the gastric mucosa.
Figure 1. Helicobacter pylori
The study further determined that the helical shape of H pylori requires relaxation of peptidoglycan cross-linking. “The crosslinks preserve the structural integrity of the bacterial wall, but if certain links are cleaved or relaxed by
animal models. The researcher is expanding the study to analyze samples from 600 patients using next-generation sequencing technology “to provide deeper coverage of bacterial communities.” The ultimate goal may be to determine if the differences in bacterial populations found in the mucosa lining the colon also exist within the luminal fraction. If so, it could mean less invasive screening for cancer and more cancers being caught earlier, when survival rates are higher. “Our findings suggest that adherent bacteria may be significant players in the development of adenomas and colorectal cancer,” the authors state. “Extension of these findings could lead to strategies to manipulate the microbiota to prevent colorectal adenomas and cancer as well as to identify individuals at high risk.” See: Shen, et al, Gut Microbes, May/ June 2010.
these proteins, it allows the rod shape to twist into a helix,” Salama said. Other disease-inducing bacteria that harbor these proteins include Vibrio cholera and Campylobacter jejuni. Thus, it seems that unlocking the keys to H pylori’s helical structure may lead to better antibiotic drugs for diseases ranging from ulcers and stomach cancer to diarrhea and cholera. “In this work, we have established H pylori as an excellent model to elucidate molecular determinants of helical cell shape in the Proteobacteria and the selective role of shape during host colonization,” the authors state. “Our discovery of a family of LytM peptidase homologs required for efficient stomach colonization by H pylori suggests new targets for antimicrobial therapy that may have efficacy in other pathogens that utilize these proteins, including Vibrio and Campylobacter species.” See: http://www.cell.com/ fulltext/S0092-8674(10)00365-X. GASTROENTEROLOGY 2010;139:367–368