Indian Journal of Microbiology

, Volume 59, Issue 4, pp 508–513 | Cite as

Acetic Acid Increased the Inactivation of Multi-drug Resistant Non-typhoidal Salmonella by Large-Scaffold Antibiotic

  • Vinicius Silva Castro
  • Bruno Serpa Vieira
  • Adelino Cunha-Neto
  • Eduardo Eustáquio de Souza Figueiredo
  • Carlos Adam Conte-JuniorEmail author
Original Research article


Salmonella is a gram-negative bacterium with intrinsic resistance to large-scaffold antibiotics due to the presence of an outer membrane. Based on the mode of action of the organic acids in outer membrane disintegration, and consequently, an enhancement in cell permeability, a combination of acetic acid and a large-scaffold antibiotic is it evaluated. Therefore, the aim of this study is to assess the combination of different levels of acetic acid with vancomycin, in order to determine whether or not the organic acid may overcome the cell wall and the intrinsic resistance in multi-drug resistant Salmonella. Screening of five wild-type Salmonella strains and one clinical strain was performed to select the strain more resistance to acid inhibition. Acetic acid was tested at 2.0, 1.75, 1.50, and 1.25% levels, separated or combined with 8 µg/mL vancomycin dose. An aliquot was collected after exposure and inoculated into the brain and heart infusion agar. The plates were counted and the data analyzed by ANOVA and a posthoc Tukey test (p < 0.05). The results indicate that 1.25 and 1.50% levels did not affect the vancomycin inactivation of multi-drug resistant Salmonella. However, at levels of 1.75 and 2.0%, an increase in microbial reduction is observed. Also, 2% level acetic acid and vancomycin had a threefold increase compared to vancomycin alone. Therefore, the use of acetic acid as prior treatment for Salmonella increased the inactivation rate of vancomycin. The combination of organic acid and antibiotics is a potential tool to overcome cases of antimicrobial resistance.


Antimicrobial drug resistance Glacial acetic acid Organic chemicals Public health Vancomycin resistance 



This study was funded by: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro—FAPERJ (Grant Number E-26/203.049/2017), Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq (Grant Number 311422/2016-0) and, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES (Grant Number 88881.169965/2018-01), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES (Visiting Professor Process: PVEX-88881.169965/2018-01) and Fundação de Amparo a Pesquisa do Estado de Mato Grosso—FAPEMAT (Grant Number 222388/2015).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    San Martín B, Lapierre L, Cornejo J, Bucarey S (2008) Characterization of antibiotic resistance genes linked to class 1 and 2 integrons in strains of Salmonella spp. isolated from swine. Can J Microbiol 54:569–576. CrossRefPubMedGoogle Scholar
  2. 2.
    Panzenhagen PHN, Cabral CC, Suffys PN, Franco RM, Rodrigues DP, Conte-Junior CA (2018) Comparative genome analysis and characterization of the Salmonella Typhimurium strain CCRJ_26 isolated from swine carcasses using whole-genome sequencing approach. Lett Appl Microbiol 66:352–359. CrossRefPubMedGoogle Scholar
  3. 3.
    Desikan P, Kumar Y, Pande HK, Jain A, Panwalkar N, Verma M, Bramhne HG, Yadav A, Mohapatra S (2009) Isolated ulcerative skin lesion caused by Salmonella Weltevreden. J Infect Dev Ctries 13:569–571. CrossRefGoogle Scholar
  4. 4.
    Wen SC, Best E, Nourse C (2017) Non-typhoidal Salmonella infections in children: review of literature and recommendations for management. J Paediatr Child Health 53:936–941. CrossRefPubMedGoogle Scholar
  5. 5.
    Muheim C, Götzke H, Eriksson AU, Lindberg S, Lauritsen I, Nørholm MHH, Daley DO (2017) Increasing the permeability of Escherichia coli using MAC13243. Sci Rep 7:17629. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Pagès J-M, Chloë J, Winterhalter M (1994) The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria. Nat Rev Microbiol 6:893–903CrossRefGoogle Scholar
  7. 7.
    Nikaido H (2003) Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 67:593–656. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Alakomi HL, Skyttä E, Saarela M, Mattila-Sandholm T, Latva-Kala K, Helander IM (2000) Lactic acid permeabilizes gram-negative bacteria by disrupting the outer membrane. Appl Environ Microbiol 66:2001–2005. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Cunha-Neto A, Carvalho LA, Carvalho RCT, Rodrigues DP, Mano SB, Figueiredo ES, Conte-Junior CA (2018) Salmonella isolated from chicken carcasses from a slaughterhouse in the state of Mato Grosso, Brazil: antibiotic resistance profile, serotyping, and characterization by repetitive sequence-based PCR system. Poult Sci 97:1373–1381. CrossRefPubMedGoogle Scholar
  10. 10.
    Hudzicki J (2009) Kirby–Bauer disk diffusion susceptibility test protocol. American Society Microbiology. Accessed 7 May 2019
  11. 11.
    Featherstone JDB, Rodgers BE (1981) Effect of acetic, lactic and other organic acids on the formation of artificial carious lesions. Caries Res 15:377–385. CrossRefPubMedGoogle Scholar
  12. 12.
    CLSI. Clinical and Laboratory Standards Institute (2016) Performance standards for antimicrobial susceptibility testing; Twenty-sixth informational supplement. CLSI document M100-S26. Clinical and Laboratory Standards Institute, WayneGoogle Scholar
  13. 13.
    Zhitnitsky D, Rose J, Lewinson O (2017) The highly synergistic, broad spectrum, antibacterial activity of organic acids and transition metals. Sci Rep 7:44554. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Yuk HG, Marshall DL (2003) Heat adaptation alters Escherichia coli O157:H7 membrane lipid composition and verotoxin production. Appl Environ Microbiol 69:5115–5119. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Ventola CL (2015) The antibiotic resistance crisis: part 1: causes and threats. Pharm Therap 40:277–283Google Scholar
  16. 16.
    Inns T, Lane C, Peters T, Dallman T, Chatt C, McFarland N, Crook P, Bishop T, Edge J, Hawker J, Elson R, Neal K, Adak GK, Cleary POC (2015) A multi-country Salmonella Enteritidis phage type 14b outbreak associated with eggs from a German producer: ‘near real-time’ application of whole genome sequencing and food chain investigations, United Kingdom, May to September 2014. Eurosurveillance 20:21098CrossRefGoogle Scholar
  17. 17.
    Mba-Jonas A, Culpepper W, Hill T, Cantu V, Loera J, Borders J, Saathoff-Huber L, Nsubuga J, Zambrana I, Dalton S, Williams I, Neil KP (2018) A multistate outbreak of human Salmonella agona infections associated with consumption of fresh, whole papayas imported from Mexico–United States, 2011. Clin Infect Dis 66:1756–1761. CrossRefPubMedGoogle Scholar
  18. 18.
    Thung TY, Radu S, Mahyudin NA, Rukayadi Y, Zakaria Z, Mazlan N, Tan BH, Lee E, Yeoh SL, Chin YZ, Tan CW, Kuan CH, Basri DF, Radzi CWJWM (2018) Prevalence, virulence genes and antimicrobial resistance profiles of Salmonella serovars from retail beef in Selangor, Malaysia. Front Microbiol 8:2697. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Watanakunakorn C (1984) Mode of action and in vitro activity of vancomycin. J Antimicrob Chemother 14:7–18CrossRefGoogle Scholar
  20. 20.
    Boneca IG, Chiosis G (2003) Vancomycin resistance: occurrence, mechanisms and strategies to combat it. Expert Opin Ther Targets 7:311–328. CrossRefPubMedGoogle Scholar
  21. 21.
    Chapman B, Ross T (2009) Escherichia coli and Salmonella enterica are protected against acetic acid, but not hydrochloric acid, by hypertonicity. Appl Environ Microbiol 75:3605–3610. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Zhou A, Kang TM, Yuan J, Beppler C, Nguyen C, Mao Z, Nguyen MQ, Yeh P, Miller JH (2015) Synergistic interactions of vancomycin with different antibiotics against Escherichia coli: trimethoprim and nitrofurantoin display strong synergies with vancomycin against wild-type E. coli. Antimicrob Agents Chemother 59:276–281. CrossRefPubMedGoogle Scholar

Copyright information

© Association of Microbiologists of India 2019

Authors and Affiliations

  1. 1.Institute of ChemistryUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil
  2. 2.College of Agronomy and Animal ScienceUniversidade Federal de Mato GrossoCuiabáBrazil
  3. 3.College of NutritionUniversidade Federal de Mato GrossoCuiabáBrazil
  4. 4.Department of Food Technology, Faculdade de VeterináriaUniversidade Federal FluminenseRio de JaneiroBrazil
  5. 5.National Institute of Health Quality ControlFundação Oswaldo CruzRio de JaneiroBrazil

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