Neisseria gonorrhoeae-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 H Chow; Sachith D Gunasinghe; Rebecca Bamert; Jian Li; Trevor Lithgow; Benjamin P Howden; Thomas Naderer

doi:10.1093/femsml/uqac013

Neisseria gonorrhoeae-derived outer membrane vesicles package β-lactamases to promote antibiotic resistance

Microlife. 2022 Jul 29:3:uqac013. doi: 10.1093/femsml/uqac013. eCollection 2022.

Authors

Subhash Dhital^{1

2}, Pankaj Deo^{1

2}, Manasa Bharathwaj^{2

3}, Kristy Horan⁴, Joshua Nickson^{1

2}, Mohammad Azad^{2

3}, Isabella Stuart^{1

2}, Seong H Chow^{1

2}, Sachith D Gunasinghe^{3

5}, Rebecca Bamert^{2

3}, Jian Li^{2

3}, Trevor Lithgow^{2

3}, Benjamin P Howden⁴, Thomas Naderer^{1

2}

Affiliations

¹ Infection Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.
² Centre to Impact AMR, Monash University, Clayton, Australia.
³ Infection Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Victoria, Australia.
⁴ Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
⁵ European Molecular Biology Laboratory (EMBL) Australia Node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.

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 bla_TEM-1B or bla_TEM-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.

Keywords: OMV; TEM-1; antimicrobial resistance; gonorrhoea; lactamase; secretion system.