| Autor: |
Bodoev I; Federal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, Russia., Malakhova M; Federal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, Russia., Bespyatykh J; Federal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, Russia., Bespiatykh D; Federal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, Russia., Arapidi G; Federal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, Russia.; Moscow Institute of Physics and Technology, State University, 141701 Dolgoprudny, Russia., Pobeguts O; Federal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, Russia., Zgoda V; Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, 119121 Moscow, Russia., Shitikov E; Federal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, Russia., Ilina E; Federal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, Russia. |
| Abstrakt: |
There is growing concern about the emergence and spread of multidrug-resistant Neisseria gonorrhoeae. To effectively control antibiotic-resistant bacterial pathogens, it is necessary to develop new antimicrobials and to understand the resistance mechanisms to existing antibiotics. In this study, we discovered the unexpected onset of drug resistance in N. gonorrhoeae caused by amino acid substitutions in the periplasmic chaperone SurA and the β-barrel assembly machinery component BamA. Here, we investigated the i19.05 clinical isolate with mutations in corresponding genes along with reduced susceptibility to penicillin, tetracycline, and azithromycin. The mutant strain NG05 ( surA mut bamA mut , and penA mut ) was obtained using the pan-susceptible n01.08 clinical isolate as a recipient in the transformation procedure. Comparative proteomic analysis of NG05 and n01.08 strains revealed significantly increased levels of other chaperones, Skp and FkpA, and some transport proteins. Efflux pump inhibition experiments demonstrated that the reduction in sensitivity was achieved due to the activity of efflux pumps. We hypothesize that the described mutations in the surA and bamA genes cause the qualitative and quantitative changes of periplasmic chaperones, which in turn alters the function of synthesized cell envelope proteins. |
