Poor Correlation of Diversified MDR Genes in Gonococci Plasmids: Does Alteration in Chromosomal DEGs, PBP2 and Target Mutations Sufficient to Widespread Multi-Resistance in Neisseria gonorrhoeae?

Abstract

Spread of ceftriaxone and ciprofloxacin resistant gonococci diseases demand new drug development as research have contradicted potent carbapenem and aminoglycoside antibiotics against Neisseria gonorrhoeae infections. Pubmed and GenBank analysis demonstrated only bla TEM and tetM genes present in N. gonorrhoeae plasmids where as in most MDR Enterobacteriaceae, hundred diversified beta-lactamase genes (blaOXA, blaCTX-M, blaCMY and blaNDM1) as well as many drug modified genes (aacA1/C1, catB3, aph, strA/B, sul1/2, aad, aph and aac(6’)-1b) are frequent in plasmids and chromosome. Thus existing knowledge on gonococci mdr genes is limited and merely few chromosomal drug efflux genes (DEGs=ermAB, mtrCDE, macAB etc.) and penicillin binding proteins (PBPs=ponA and penA) have assigned as cause of multi-resistance. It appeared that N. gonorrhoeae had limited life cycle outside the host limiting conjugation with other MDR-bacteria to acquire mdr genes easily. BLAST-search confirmed that every MDR N. gonorrhoeae genome did carry mtrD RND transporter gene linked to mtrC outer membrane efflux gene (MFS) similar to P. aeruginosa mexAB-family transporters. Further, macA/B transporters are involved in macrolide drug efflux and many mutations in penA, gyrA, mtrR and porB genes are maximum in MDR strains although mtrF and norA efflux genes are infrequent. We argue that plasmid mediated multi-resistance in gonococcal diseases needs to be reinvestigated and mutation theory (penA, gyrA, mtrR) may not sufficient to prove the worldwide spread of multi-drug resistant STDs.