<i>Neisseria gonorrhoeae</i>-derived outer membrane vesicles package β-lactamases to promote antibiotic resistance
Subhash Dhital, Pankaj Deo, Manasa Bharathwaj, Kristy Horan, Joshua Nickson, Mohammad Azad, Isabella Stuart, Seong Hoong Chow, Sachith D. Gunasinghe, Rebecca S. Bamert, Jian Li, Trevor Lithgow, Benjamin P. Howden, Thomas Naderer
Abstract
Abstract Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhoea. The treatment of gonorrhoea is becoming increasingly challenging, as N. gonorrhoeae 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 N. gonorrhoeae survives an initial exposure to β-lactams before acquiring resistance genes remains to be understood. Here, using a panel of clinical isolates of N. gonorrhoeae we show that the β-lactamase enzyme is packaged into outer membrane vesicles (OMVs) by strains expressing blaTEM-1B or blaTEM-106, which protects otherwise susceptible clinical isolates from the β-lactam drug amoxycillin. We characterized the phenotypes of these clinical isolates of N. gonorrhoeae 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, N. gonorrhoeae strains secret antibiotic degrading enzymes via OMVs enabling survival of otherwise susceptible bacteria.