<i>Neisseria gonorrhoeae</i>-derived outer membrane vesicles package β-lactamases to promote antibiotic resistance

Abstract

<i>Neisseria gonorrhoeae</i> causes the sexually transmitted disease gonorrhoea. The treatment of gonorrhoea is becoming increasingly challenging, as <i>N. gonorrhoeae</i> has developed resistance to antimicrobial agents routinely used in the clinic. Resistance to penicillin is wide-spread partly due to the acquisition of β-lactamase genes. How <i>N. gonorrhoeae</i> survives an initial exposure to β-lactams before acquiring resistance genes remains to be understood. Here, using a panel of clinical isolates of <i>N. gonorrhoeae</i> we show that the β-lactamase enzyme is packaged into outer membrane vesicles (OMVs) by strains expressing <i>bla</i>_TEM-1B or <i>bla</i>_TEM-106, which protects otherwise susceptible clinical isolates from the β-lactam drug amoxycillin. We characterized the phenotypes of these clinical isolates of <i>N. gonorrhoeae</i> and the time courses over which the cross-protection of the strains is effective. Imaging and biochemical assays suggest that OMVs promote the transfer of proteins and lipids between bacteria. Thus, <i>N. gonorrhoeae</i> strains secret antibiotic degrading enzymes via OMVs enabling survival of otherwise susceptible bacteria.