![]() ![]() Modification of the antibiotic target is one of the ways in which bacteria protect themselves from the lethal effects of their own antibiotics. ![]() ![]() It has become clear that the environment is the source of an almost unlimited diversity of antibiotic resistance elements that are both extremely specific (e.g., inactivating enzymes) and broad (e.g., efflux systems), enabling the bacterium to counteract most antibiotics. Over time, bacteria acquire resistance elements reflecting their current and past encounters with antibiotic producers ( 4). It has been suggested that horizontal gene transfer (HGT) of entire groups of genes plays a role in the evolution of BGCs and resistance. Over time, a copy of the self-resistance determinant integrates into the BGC, leading to coregulated expression, often through incorporation into the same operon. Functional, genomic, and phylogenetic analyses of oatA revealed the coevolution of antibiotic production and self-resistance as ancient feature of this particular niche in soil invertebrates without resistance dissemination.īacteria carrying BGCs encoding antimicrobial agents require protective mechanisms against these compounds ( 3), to ensure that their production leads to the destruction of other susceptible microorganisms without causing suicide of the producing bacterium. In vitro acetylation and LC-MS/MS analyses showed that OatA targeted the side chain amino group of ODL rare amino acids, leading to a loss of translation inhibition and antibacterial properties. In this study, we cloned the ODL-biosynthetic gene cluster of the symbiont by recombineering and showed that the N-acetyltransferase-encoding gene, oatA, is responsible for ODL resistance. Like other antimicrobial producers, ODL-producing Xenorhabdus nematophila has mechanisms of self-protection. These natural peptides are produced by Xenorhabdus nematophila, a bacterial symbiont of entomopathogenic nematodes well known to produce large amounts of specialized secondary metabolites. ODLs are 10-mer linear cationic peptides inhibiting bacterial translation by binding to the small subunit of the ribosome. IMPORTANCE Odilorhabdins (ODLs) constitute a novel antibiotic family with promising properties for treating problematic multidrug-resistant Gram-negative bacterial infections. ![]() This work highlights the coevolution of antibiotic production and self-resistance as ancient features of this unique tripartite complex of host-vector-symbiont interactions without odl-BGC dissemination by lateral gene transfer. nematophila and a specific phylogenetic clade of Photorhabdus. Functional, genomic, and phylogenetic analyses of oatA revealed an exclusive cis-link to the odilorhabdin BGC, found only in X. In vitro acetylation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses showed that OatA targeted the side chain amino group of ODL rare amino acids, leading to a loss of translation inhibition and antibacterial properties. In this study, we cloned the 44.5-kb odl biosynthetic gene cluster ( odl-BGC) of the symbiont by recombineering and showed that the N-acetyltransferase-encoding gene, oatA, is responsible for ODL resistance. ODL-producing Xenorhabdus nematophila symbionts have mechanisms of self-protection. These bioactive secondary metabolites are produced by entomopathogenic bacterial symbiont Xenorhabdus ( Morganellaceae), vectored by the soil-dwelling nematodes. Natural odilorhabdins (ODLs) constitute a new family of 10-mer linear cationic peptide antibiotics inhibiting bacterial translation by binding to the 30S subunit of the ribosome. A direct link has been established between antimicrobial self-resistance determinants of antibiotic producers, environmental bacteria, and clinical pathogens. Antibiotic resistance is an increasing threat to human health. ![]()
0 Comments
Leave a Reply. |