doi: 10.1128/AEM.03946-15, Perkins, D. N., Pappin, D. J., Creasy, D. M., and Cottrell, J. S. (1999). The datasets generated for this study can be found in the https://chorusproject.org/pages/authentication.html#/login; accession number PXD020384. Copyright © 2020 Elsevier B.V. or its licensors or contributors. Membrane permeability remained unchanged (Supplementary Figure 4). doi: 10.1096/fj.04-1815fje, Kohanski, M. A., Dwyer, D. J., and Collins, J. J. Conversely, proteins associated with stress response and oxidative stress defenses, as well as central carbon metabolism, were downregulated (Table 1 and Supplementary Table 1). Given that oxidative stress and redox disbalance has been implicated in antibiotics lethality (Kohanski et al., 2007; Dwyer et al., 2014), we hypothesized that H2S potentiates antibiotic-induced oxidative-stress. 12, 1061–1064. (C) Effect of H2S on the membrane potential. Rev. Rev. Percentages of antibiotic susceptibility in Acinetobacter calcoaceticus ... Our findings show that the predominant non-baumannii Acinetobacter spp. 21, 13–17. H2S has been shown to render multiple bacterial species tolerant to oxidative stress and various classes of antibiotics (Shatalin et al., 2011). A., and Ur Rehman, S. (2018). Introduction. RLU is reported as a percentage of untreated cells. We treated cultures of A. baumannii with increasing concentration of NaHS alone, or in combination with a fixed concentration of antibiotic. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Instead, we propose that H2S-releasing compounds could be used in combination with antibiotics to sensitize AMR bacteria like A. baumannii. A similar trend was observed with colistin (Figure 2B). Multidrug-resistant Acinetobacter baumannii: differential adherence to HEp-2 and A-549 cells. The expression of superoxide dismutase protein, a major oxidant detoxifying enzyme, was significantly reduced. This study aimed to investigate antibiotic resistance patterns and resistance-related, genes in clinical isolates of Acinetobacter baumannii. Antibiotics and sodium hydrosulfide (NaHS) were purchased from Gold Biotechnology and Sigma-Aldrich, respectively. doi: 10.1371/journal.pone.0104206, Fu, L. H., Wei, Z. Our findings suggest that H2S cannot be regarded as a universal protective molecule against antibiotic insult. doi: 10.1016/j.cell.2007.06.049, Luhachack, L., and Nudler, E. (2014). Hydrogen sulfide cytotoxic effects, notably caused by its interaction with iron-containing protein, are well documented (Reiffenstein et al., 1992). Hydrogen sulfide induces direct radical-associated DNA damage. Bacterial gasotransmitters: an innate defense against antibiotics. Physiol. Sci. NLM H2S: a universal defense against antibiotics in bacteria. doi: 10.1089/ars.2008.2282, Kimura, Y., and Kimura, H. (2004). NIH 44, 827–834. doi: 10.1016/j.freeradbiomed.2019.04.006. AS received support from the Singapore—MIT Alliance (SMA) Graduate Fellowship. Acinetobacter baumannii is a Gram-negative, glucose-non-fermenting, oxidase-negative coccobacillus, most commonly associated with the hospital settings. While some important pathogenic bacteria encode the H2S biosynthetic pathway, others do not (Luhachack and Nudler, 2014). Br. Longev. doi: 10.1089/ars.2009.2938, Weikum, J., Ritzmann, N., Jelden, N., Klöckner, A., Herkersdorf, S., Josten, M., et al. By continuing you agree to the use of cookies. The labels for the second run were as follows 129C-BioRep3-Untreated, 130N-BioRep3-NAHS_Colistin_Treated, 130C – BioRep3-Colistin_Treated, and 131 – BioRep3-NAHS_Treated. 11:1875. doi: 10.3389/fmicb.2020.01875. H2S antifungal effects on Aspergillus niger and Penicillium italicum were mediated by reduction in superoxide dismutase (SOD) and catalase (CAT) activities, and increased ROS formation (Fu et al., 2014). 83, 356–365. |, Antimicrobials, Resistance and Chemotherapy, https://chorusproject.org/pages/authentication.html#/login, https://www.frontiersin.org/articles/10.3389/fmicb.2020.01875/full#supplementary-material, https://www.uniprot.org/proteomes/UP000032746, https://evolve.elsevier.com/cs/product/9780323030656?role=student, Creative Commons Attribution License (CC BY). Dusek, P., Dezortova, M., and Wuerfel, J. Natl. We are thankful to Dr. Andrea Kwa (Duke-NUS & Singapore General Hospital) and Dr. Lim Tze Peng (Duke-NUS & Singapore General Hospital) for providing A. baumannii clinical isolate. On the contrary, we showed that A. baumannii treated with H2S-releasing agent displayed hypersensitivity to different antibiotics with unrelated mechanisms of actions. Hydrogen sulfide: the third gasotransmitter in biology and medicine. 69, 626–636. Acinetobacter baumannii Bouvet and Grimont (ATCC® BAA-2093TM), clinical isolate #8879 (curtesy of Dr. Andrea Kwa and Dr. Lim Tze Peng, Singapore General Hospital (SGH), Singapore), and Klebsiella pneumoniae (Schroeter) Trevisan (ATCC® 13883TM) were streaked on Luria-Bertani (LB)-agar plates. Microbiol. To our knowledge, this is the first report of H2S-induced antibiotic sensitization and resistance reversion.

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