N-Acetyl Cysteine Exhibits Antimicrobial and Anti-virulence Activity Against Salmonella Enterica

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2025 Jan 8

PMID 39775338

Authors

Selwan Hamed

Mohamed Emara

Payman Tohidifar

Christopher V Rao

Affiliations

Soon will be listed here.

Abstract

Salmonella enterica is a common foodborne pathogen that causes intestinal illness varying from mild gastroenteritis to life-threatening systemic infections. The frequency of outbreaks due to multidrug-resistant Salmonella has been increased in the past few years with increasing numbers of annual deaths. Therefore, new strategies to control the spread of antimicrobial resistance are required. In this work, we found that N-acetyl cysteine (NAC) inhibits S. enterica at MIC of 3 mg ml-1 and synergistically activates the bactericidal activities of common antibiotics from three-fold for ampicillin and apramycin up to1000-fold for gentamycin. In addition, NAC inhibits the expression of virulence genes at sub-inhibitory concentrations in a dose-dependent manner. The whole-genome sequencing revealed that continuous exposure of S. enterica to NAC leads to the development of resistance; these resistant strains are attenuated for virulence. These results suggest that NAC may be a promising adjuvant to antibiotics for treating S. enterica in combination with other antibiotics.

References

Aypak A, Kutta Celik A, Aypak C, Cikman O . Multidrug resistant typhoid fever outbreak in Ercek Village-Van, Eastern Anatolia, Turkey: clinical profile, sensitivity patterns and response to antimicrobials. Trop Doct. 2010; 40(3):160-2. DOI: 10.1258/td.2010.090438. View

Kage H, Takaya A, Ohya M, Yamamoto T . Coordinated regulation of expression of Salmonella pathogenicity island 1 and flagellar type III secretion systems by ATP-dependent ClpXP protease. J Bacteriol. 2008; 190(7):2470-8. PMC: 2293192. DOI: 10.1128/JB.01385-07. View

. Multistate outbreak of human Salmonella infections caused by contaminated dry dog food--United States, 2006-2007. MMWR Morb Mortal Wkly Rep. 2008; 57(19):521-4. View

Chen F, Zhou Y . Hepatic effect of NAC on sevear acute pancteatise of rats. Asian Pac J Trop Med. 2014; 7(2):141-3. DOI: 10.1016/S1995-7645(14)60010-9. View

Cao R, Teskey G, Islamoglu H, Abrahem R, Munjal S, Gyurjian K . Characterizing the Effects of Glutathione as an Immunoadjuvant in the Treatment of Tuberculosis. Antimicrob Agents Chemother. 2018; 62(11). PMC: 6201097. DOI: 10.1128/AAC.01132-18. View

Wang X, Koirala S, Aldridge P, Rao C . Two Tandem Mechanisms Control Bimodal Expression of the Flagellar Genes in Salmonella enterica. J Bacteriol. 2020; 202(13). PMC: 7283601. DOI: 10.1128/JB.00787-19. View

Li H . A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics. 2011; 27(21):2987-93. PMC: 3198575. DOI: 10.1093/bioinformatics/btr509. View

Sansone R, Sansone L . Getting a Knack for NAC: N-Acetyl-Cysteine. Innov Clin Neurosci. 2011; 8(1):10-4. PMC: 3036554. View

Riise G, Qvarfordt I, Larsson S, Eliasson V, Andersson B . Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro. Respiration. 2000; 67(5):552-8. DOI: 10.1159/000067473. View

10.

Wain J, Hendriksen R, Mikoleit M, Keddy K, Ochiai R . Typhoid fever. Lancet. 2014; 385(9973):1136-45. PMC: 11567078. DOI: 10.1016/S0140-6736(13)62708-7. View

11.

Saini S, Ellermeier J, Slauch J, Rao C . The role of coupled positive feedback in the expression of the SPI1 type three secretion system in Salmonella. PLoS Pathog. 2010; 6(7):e1001025. PMC: 2912647. DOI: 10.1371/journal.ppat.1001025. View

12.

Blasi F, Page C, Rossolini G, Pallecchi L, Matera M, Rogliani P . The effect of N-acetylcysteine on biofilms: Implications for the treatment of respiratory tract infections. Respir Med. 2016; 117:190-7. DOI: 10.1016/j.rmed.2016.06.015. View

13.

Florez-Cuadrado D, Moreno M, Ugarte-Ruiz M, Dominguez L . Antimicrobial Resistance in the Food Chain in the European Union. Adv Food Nutr Res. 2018; 86:115-136. DOI: 10.1016/bs.afnr.2018.04.004. View

14.

Goswami M, Jawali N . N-acetylcysteine-mediated modulation of bacterial antibiotic susceptibility. Antimicrob Agents Chemother. 2010; 54(8):3529-30. PMC: 2916349. DOI: 10.1128/AAC.00710-10. View

15.

Manniello M, Del Gaudio P, Aquino R, Russo P . Clarithromycin and N-acetylcysteine co-spray-dried powders for pulmonary drug delivery: A focus on drug solubility. Int J Pharm. 2017; 533(2):463-469. DOI: 10.1016/j.ijpharm.2017.03.079. View

16.

Kokai D, Mosolygo T, Virok D, Endresz V, Burian K . -acetyl-cysteine increases the replication of and prolongs the clearance of the pathogen from mice. J Med Microbiol. 2018; 67(5):702-708. DOI: 10.1099/jmm.0.000716. View

17.

Yombi J, Martins L, Vandercam B, Rodriguez-Villalobos H, Robert A . Clinical features and outcome of typhoid fever and invasive non-typhoidal salmonellosis in a tertiary hospital in Belgium: analysis and review of the literature. Acta Clin Belg. 2015; 70(4):265-71. DOI: 10.1179/2295333715Y.0000000016. View

18.

Li H, Durbin R . Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics. 2010; 26(5):589-95. PMC: 2828108. DOI: 10.1093/bioinformatics/btp698. View

19.

Hamed S, Wang X, Shawky R, Emara M, Aldridge P, Rao C . Synergistic action of SPI-1 gene expression in Salmonella enterica serovar typhimurium through transcriptional crosstalk with the flagellar system. BMC Microbiol. 2019; 19(1):211. PMC: 6727558. DOI: 10.1186/s12866-019-1583-7. View

20.

Monti D, Zabrecky G, Kremens D, Liang T, Wintering N, Bazzan A . N-Acetyl Cysteine Is Associated With Dopaminergic Improvement in Parkinson's Disease. Clin Pharmacol Ther. 2019; 106(4):884-890. DOI: 10.1002/cpt.1548. View