When our immune system wages war against invading gut pathogens, our beneficial bacteria need to evade the attack. According to a report in Science, removing phosphate groups from the lipopolysaccharide exterior of their cells is one defense strategy commensal gut bacteria use to avoid the immune system’s friendly fire (2015, DOI: 10.1126/science.1260580). A team of researchers led by Andrew Goodman and Thomas Cullen at Yale University set out to discover why common, friendly gut bacteria, such as those in the Bacteroidetes phylum, are around 1,000-fold more resistant to attacks from our innate immune system than many invading pathogens. They found that when the innate immune system produces cationic antimicrobial peptides, a common set of chemical weapons that seek out negatively charged bacterial cells, commensal Bacteroidetes bacteria persist by removing a phosphate group from the lipopolysaccharide coating of their cells. Removal of the phosphate groups helps the commensal bacteria neutralize the negative charge of the cells. This process reduces binding of the positively charged antimicrobial peptides and thus prevents the membrane disruption caused by the immune peptides.