Protective umbrella of antibacterial peptide and beneficial flora

In part, mammalian hosts fight against intestinal infection by releasing antimicrobial peptides that destroy bacterial membranes But until now, it is not clear how the beneficial microorganisms survive in the released antimicrobial peptides and maintain a stable population in the gut According to the results of a new research paper published in the January 8 issue of science, a major group of symbiotic intestinal bacteria: the Bacteroidetes avoids collateral damage by virtue of only one gene, which encodes an enzyme that changes lipopolysaccharide (LPS) in bacterial cell membrane Andy Goodman, co-author of the paper and assistant professor of the Department of microbial etiology at Yale University School of medicine, said: "in general, many aspects of the immune response target some microbial characteristics, rather than some specific factors that only exist on pathogens We don't understand how the human body can maintain the stability of symbiotic bacteria under the same conditions of eliminating pathogens while having a seemingly extensive host response " Sarkis Mazmanian, a microbiologist at Caltech, who was not involved in the study, said: "this work has been very well done, identifying specific genetic sites, what it does to LPS, and how it regulates long-term stability and adaptability This will enhance our understanding of the mechanism of association between intestinal microorganisms and tissues " Previous studies have elucidated the mechanism by which some pathogens escape antimicrobial peptides But researchers see antimicrobial peptide resistance as a virulence factor, not a characteristic of the microbiome "Most people didn't expect symbionts to be resistant to antimicrobial peptides," said Charles Bevins of the University of California Davis School of medicine, who was not involved in the new study Scientists believe that antimicrobial peptides only kill symbionts in parts of the gut so that their populations can recover, or that symbionts stay away from the cells that release antimicrobial peptides In recent years, however, some researchers, including Mazmanian, have confirmed that symbionts are closely related to the mucosal layer of the gut, where they may be in close contact with antimicrobial peptides To investigate the mechanism of bacterial retention in the gut, Goodman and colleagues exposed 17 symbiotic communities and four intestinal pathogens to a variety of positively charged antimicrobial peptides The researchers found that symbionts living in the three major groups of gut can survive at higher concentrations of antimicrobial peptides than pathogens In order to understand the mechanism of symbiotic bacteria protecting themselves, the researchers randomly mutated some genes of 5 symbiotic Bacteroides at various sites, and screened bacteria that lost antimicrobial peptide resistance Although each bacterium has multiple genes to help it resist antimicrobial peptides, only one is shared by all five Because it is similar to a phosphatase coding gene found in some antimicrobial peptide resistant pathogens, the researchers named the gene lpxf Phosphatase lpxf can remove a negatively charged phosphate from LPS that helps to form bacterial membranes This charge transformation makes it difficult for the positive charge antimicrobial peptide to bind to the bacterial membrane and destroy it This phosphate, which is necessary for the construction of cell membranes, becomes superfluous when bacteria mature For further research, the researchers removed lpxf from antimicrobial peptide resistant bacteria and tested their adaptability in mice infected with intestinal tract Because Bacteroides the taiotaomicron is easy to carry out genetic manipulation, they chose this kind of bacteria Then they let a variety of pleomorphic Bacteroides migrate to sterile mice, some bacteria deleted lpxf, some bacteria were wild-type, and some bacteria lpxf was deleted and replaced They then infected mice with the intestinal pathogen Citrobacter to induce the release of antimicrobial peptides In the absence of intestinal pathogens, the bacteria deleted by lpxf were very good, but were rapidly exceeded in infected mice Chemical induction of antimicrobial peptides showed similar effects The researchers also saw that bacteria carrying functional lpxf outperformed mutants and had more diverse gut symbionts Finally, the researchers obtained microbes from the feces of 12 people and exposed them to antimicrobial peptides They also found that many symbionts could survive when exposed to antimicrobial peptides, while some members of Proteobacteria phylum, including many pathogens, did not perform well Although the researchers have done most of the research in Bacteroides polymorpha, they point out that so far all of the sequencing Bacteroides that live in humans have lpxf gene versions Goodman was surprised to find that an enzyme gave bacteria so much resistance to antimicrobial peptides "We have speculated that the interaction of microbial hosts is so complex that a single factor can't do anything, but what we see is not so at all." Further research is needed to elucidate why widespread symbiotic bacteria, not just Bacteroides, can resist some host defense mechanisms And Bacteroides may also use a variety of methods against host defense "This study identified an enzyme that affects the interaction of host microorganisms on one hand, but we don't think this is the only example," Goodman said It is hoped that this study will open a door to a better understanding of other mechanisms by which symbiotic microorganisms can interact with pathogens and hosts "