Advertisement

Applied Microbiology and Biotechnology

, Volume 102, Issue 5, pp 2323–2335 | Cite as

4-Hydroxybenzaldehyde sensitizes Acinetobacter baumannii to amphenicols

  • Bora Shin
  • Chulwoo Park
  • James A. Imlay
  • Woojun Park
Applied microbial and cell physiology

Abstract

Bacterial metabolism modulated by environmental chemicals could alter antibiotic susceptibility. 4-Hydroxybenzaldehyde (4-HBA), which cannot support the growth of Acinetobacter baumannii, exhibited synergism only with amphenicol antibiotics including chloramphenicol (CAM) and thiamphenicol. Interestingly, this synergistic effect was not observed with other growth-supporting, structurally similar compounds such as 4-hydroxybenzoate. Transcriptomic analysis demonstrated that genes involved in protocatechuate metabolism (pca genes) and osmotic stress (bet genes) were significantly upregulated by 4-HBA and CAM treatment. The 14C-labeled CAM influx was lower in a pcaK1 (encoding a transporter of protocatechuate) deletion mutant and was higher in the pcaK1 overexpressing cells relative to that in the wild type upon 4-HBA treatment. Our kinetic data using 14C-labeled CAM clearly showed that CAM uptake is possibly through facilitated diffusion. Deletion of pcaK1 did not result in the elimination of CAM influx, indicating that CAM does not enter only through PcaK1. The amount of 4-HBA in the culture supernatant was, however, unaffected during the test conditions, validating that it was not metabolized by the bacteria. CAM resistant A. baumannii cells derived by serial passages through CAM-amended media exhibited lower level of pcaK1 gene expression. These results led us to conclude that the activation of PcaK1 transporter is probably linked to cellular CAM susceptibility. This is the first report showing a relationship between CAM influx and aromatic compound metabolism in A. baumannii.

Keywords

Acinetobacter Synergistic compound Plant extract Chloramphenicol Synergism Phenolic compound 4-Hydroxybenzaldehyde 

Notes

Acknowledgements

This work was supported by a National Research Foundation of Korea (NRF) grant to WP funded by the Korean government (MSIP) (No. NRF-2017R1A2B4005838). BS was supported by a Korea University Grant.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

253_2018_8791_MOESM1_ESM.pdf (629 kb)
ESM 1 (PDF 628 kb)

References

  1. Anju S, Kumar NS, Krishnakumar B, Kumar BS (2015) Synergistic combination of violacein and azoles that leads to enhanced killing of major human pathogenic dermatophytic fungi Trichophyton rubrum. Front Cell Infect Microbiol 5:57.  https://doi.org/10.3389/fcimb.2015.00057 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Audrain B, Farag MA, Ryu CM, Ghigo JM (2015) Role of bacterial volatile compounds in bacterial biology. FEMS Microbiol Rev 39(2):222–233.  https://doi.org/10.1093/femsre/fuu013 CrossRefPubMedGoogle Scholar
  3. Bernardini ML, Fontaine A, Sansonetti PJ (1990) The two-component regulatory system ompR-envZ controls the virulence of Shigella flexneri. J Bacteriol 172(11):6274–6281.  https://doi.org/10.1128/jb.172.11.6274-6281.1990 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Biswas T, Houghton JL, Garneau-Tsodikova S, Tsodikov OV (2012) The structural basis for substrate versatility of chloramphenicol acetyltransferase CATI. Protein Sci 21(4):520–530.  https://doi.org/10.1002/pro.2036 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Cohen BE (2014) Functional linkage between genes that regulate osmotic stress responses and multidrug resistance transporters: challenges and opportunities for antibiotic discovery. Antimicrob Agents Chemother 58(2):640–646.  https://doi.org/10.1128/AAC.02095-13 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Coyne S, Rosenfeld N, Lambert T, Courvalin P, Perichon B (2010) Overexpression of resistance-nodulation-cell division pump AdeFGH confers multidrug resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 54(10):4389–4393.  https://doi.org/10.1128/AAC.00155-10 CrossRefPubMedPubMedCentralGoogle Scholar
  7. Damier-Piolle L, Magnet S, Bremont S, Lambert T, Courvalin P (2008) AdeIJK, a resistance-nodulation-cell division pump effluxing multiple antibiotics in Acinetobacter baumannii. Antimicrob Agents Chemother 52(2):557–562.  https://doi.org/10.1128/AAC.00732-07 CrossRefPubMedGoogle Scholar
  8. Dimarco AA, Averhoff B, Ornston LN (1993) Identification of the transcriptional activator pobR and characterization of its role in the expression of pobA, the structural gene for p-hydroxybenzoate hydroxylase in Acinetobacter calcoaceticus. J Bacteriol 175(14):4499–4506.  https://doi.org/10.1128/jb.175.14.4499-4506.1993 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Dupont M, Pages JM, Lafitte D, Siroy A, Bollet C (2005) Identification of an OprD homologue in Acinetobacter baumannii. J Proteome Res 4(6):2386–2390.  https://doi.org/10.1021/pr050143q CrossRefPubMedGoogle Scholar
  10. Falagas ME, Kopterides P (2007) Old antibiotics for infections in critically ill patients. Curr Opin Crit Care 13(5):592–597.  https://doi.org/10.1097/MCC.0b013e32827851d7 CrossRefPubMedGoogle Scholar
  11. Falagas ME, Grammatikos AP, Michalopoulos A (2008) Potential of old-generation antibiotics to address current need for new antibiotics. Expert Rev Anti-Infect Ther 6(5):593–600.  https://doi.org/10.1586/14787210.6.5.593 CrossRefPubMedGoogle Scholar
  12. Gagniere H, Di Martino P (2004) Effects of antibiotics on Pseudomonas aeruginosa NK125502 and Pseudomonas fluorescens MF0 biofilm formation on immobilized fibronectin. J Chemother 16(3):244–247.  https://doi.org/10.1179/joc.2004.16.3.244 CrossRefPubMedGoogle Scholar
  13. Gallucci MN, Oliva M, Casero C, Dambolena J, Luna A, Zygadlo J, Demo M (2009) Antimicrobial combined action of terpenes against the food-borne microorganisms Escherichia coli, Staphylococcus aureus and Bacillus cereus. Flavour Fragr J 24(6):348–354.  https://doi.org/10.1002/ffj.1948 CrossRefGoogle Scholar
  14. Geisinger E, Isberg RR (2015) Antibiotic modulation of capsular exopolysaccharide and virulence in Acinetobacter baumannii. PLoS Pathog 11(2):e1004691.  https://doi.org/10.1371/journal.ppat.1004691 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Gerischer U, Segura A, Ornston LN (1998) PcaU, a transcriptional activator of genes for protocatechuate utilization in Acinetobacter. J Bacteriol 180:1512–1524PubMedPubMedCentralGoogle Scholar
  16. Goh HM, Beatson SA, Totsika M, Moriel DG, Phan MD, Szubert J, Runnegar N, Sidjabat HE, Paterson DL, Nimmo GR, Lipman J, Schembri MA (2013) Molecular analysis of the Acinetobacter baumannii biofilm-associated protein. Appl Environ Microbiol 79(21):6535–6543.  https://doi.org/10.1128/AEM.01402-13 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Gopal R, Kim YG, Lee JH, Lee SK, Chae JD, Son BK, Seo CH, Park Y (2014) Synergistic effects and antibiofilm properties of chimeric peptides against multidrug-resistant Acinetobacter baumannii strains. Antimicrob Agents Chemother 58(3):1622–1629.  https://doi.org/10.1128/AAC.02473-13 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Harwood CS, Nichols NN, Kim MK, Ditty JL, Parales RE (1994) Identification of the pcaRKF gene cluster from Pseudomonas putida: involvement in chemotaxis, biodegradation, and transport of 4-hydroxybenzoate. J Bacteriol 176(21):6479–6488.  https://doi.org/10.1128/jb.176.21.6479-6488.1994 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Hossain MA, Park JY, Kim JY, Suh JW, Park SC (2014, 2014) Synergistic effect and antiquorum sensing activity of Nymphaea tetragona (water lily) extract. Biomed Res Int:562173.  https://doi.org/10.1155/2014/562173
  20. Kim J, Shin B, Park C, Park W (2017) Indole-induced activities of β-lactamase and efflux pump confer ampicillin resistance in Pseudomonas putida KT2440. Front Microbiol 8:433.  https://doi.org/10.3389/fmicb.2017.00433 PubMedPubMedCentralGoogle Scholar
  21. Lamark T, Røkenes TP, McDougall J, Strøm AR (1996) The complex bet promoters of Escherichia coli: regulation by oxygen (ArcA), choline (BetI), and osmotic stress. J Bacteriol 178(6):1655–1662.  https://doi.org/10.1128/jb.178.6.1655-1662.1996 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Linares JF, Moreno R, Fajardo A, Martinez-Solano L, Escalante R, Rojo F, Martínez JL (2010) The global regulator Crc modulates metabolism, susceptibility to antibiotics and virulence in Pseudomonas aeruginosa. Environ Microbiol 12(12):3196–3212.  https://doi.org/10.1111/j.1462-2920.2010.02292.x CrossRefPubMedGoogle Scholar
  23. Magnet S, Courvalin P, Lambert T (2001) Resistance-nodulation-cell division-type efflux pump involved in aminoglycoside resistance in Acinetobacter baumannii strain BM4454. Antimicrob Agents Chemother 45(12):3375–3380.  https://doi.org/10.1128/AAC.45.12.3375-3380.2001 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Martinez JL, Rojo F (2011) Metabolic regulation of antibiotic resistance. FEMS Microbiol Rev 35(5):768–789.  https://doi.org/10.1111/j.1574-6976.2011.00282.x CrossRefPubMedGoogle Scholar
  25. Mussi MA, Limansky AS, Viale AM (2005) Acquisition of resistance to carbapenems in multidrug-resistant clinical strains of Acinetobacter baumannii: natural insertional inactivation of a gene encoding a member of a novel family of beta-barrel outer membrane proteins. Antimicrob Agents Chemother 49(4):1432–1440.  https://doi.org/10.1128/AAC.49.4.1432-1440.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Nagoshi C, Shiota S, Kuroda T, Hatano T, Yoshida T, Kariyama R, Tsuchiya T (2006) Synergistic effect of [10]-gingerol and aminoglycosides against vancomycin-resistant enterococci (VRE). Biol Pharm Bull 29(3):443–447.  https://doi.org/10.1248/bpb.29.443 CrossRefPubMedGoogle Scholar
  27. Nikaido H (1994) Porins and specific diffusion channels in bacterial outer membranes. J Biol Chem 269(6):3905–3908PubMedGoogle Scholar
  28. Nitzan O, Suponitzky U, Kennes Y, Chazan B, Raul R, Colodner R (2010) Is chloramphenicol making a comeback? Isr Med Assoc J 12(6):371–374PubMedGoogle Scholar
  29. Pao SS, Paulsen IT, Saier MH Jr (1998) Major facilitator superfamily. Microbiol Mol Biol Rev 62(1):1–34PubMedPubMedCentralGoogle Scholar
  30. Pei RS, Zhou F, Ji BP, Xu J (2009) Evaluation of combined antibacterial effects of eugenol, cinnamaldehyde, thymol, and carvacrol against E. coli with an improved method. J Food Sci 74(7):M379–M383.  https://doi.org/10.1111/j.1750-3841.2009.01287.x CrossRefPubMedGoogle Scholar
  31. Pritchard JR, Bruno PM, Gilbert LA, Capron KL, Lauffenburger DA, Hemann MT (2013) Defining principles of combination drug mechanisms of action. Proc Natl Acad Sci U S A 110(2):E170–E179.  https://doi.org/10.1073/pnas.1210419110 CrossRefPubMedGoogle Scholar
  32. Rada BK, Geiszt M, Káldi K, Timár C, Ligeti E (2004) Dual role of phagocytic NADPH oxidase in bacterial killing. Blood 104(9):2947–2953.  https://doi.org/10.1182/blood-2004-03-1005 CrossRefPubMedGoogle Scholar
  33. Rajamohan G, Srinivasan VB, Gebreyes WA (2010) Novel role of Acinetobacter baumannii RND efflux transporters in mediating decreased susceptibility to biocides. J Antimicrob Chemother 65(2):228–232.  https://doi.org/10.1093/jac/dkp427 CrossRefPubMedGoogle Scholar
  34. Roca I, Marti S, Espinal P, Martinez P, Gibert I, Vila J (2009) CraA, a major facilitator superfamily efflux pump associated with chloramphenicol resistance in Acinetobacter baumannii. Antimicrob Agents Chemother 53(9):4013–4014.  https://doi.org/10.1128/AAC.00584-09 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Saier MH Jr (2000) Families of transmembrane sugar transport proteins. Mol Microbiol 35(4):699–710.  https://doi.org/10.1046/j.1365-2958.2000.01759.x CrossRefPubMedGoogle Scholar
  36. Shin B, Park W (2015) Synergistic effect of oleanolic acid on aminoglycoside antibiotics against Acinetobacter baumannii. PLoS One 10(9):e0137751.  https://doi.org/10.1371/journal.pone.0137751 CrossRefPubMedPubMedCentralGoogle Scholar
  37. Siroy A, Molle V, Lemaitre-Guillier C, Vallenet D, Pestel-Caron M, Cozzone AJ, Jouenne T, Dé E (2005) Channel formation by CarO, the carbapenem resistance-associated outer membrane protein of Acinetobacter baumannii. Antimicrob Agents Chemother 49(12):4876–4883.  https://doi.org/10.1128/AAC.49.12.4876-4883.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Smani Y, Pachon J (2013) Loss of the OprD homologue protein in Acinetobacter baumannii: impact on carbapenem susceptibility. Antimicrob Agents Chemother 57(1):677.  https://doi.org/10.1128/AAC.01277-12 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Smani Y, Dominguez-Herrera J, Pachon J (2013) Association of the outer membrane protein Omp33 with fitness and virulence of Acinetobacter baumannii. J Infect Dis 208(10):1561–1570.  https://doi.org/10.1093/infdis/jit386 CrossRefPubMedGoogle Scholar
  40. Smani Y, Fabrega A, Roca I, Sanchez-Encinales V, Vila J, Pachon J (2014) Role of OmpA in the multidrug resistance phenotype of Acinetobacter baumannii. Antimicrob Agents Chemother 58(3):1806–1808.  https://doi.org/10.1128/AAC.02101-13 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Sood S (2016) Chloramphenicol—a potent armament against multi-drug resistant (MDR) Gram negative bacilli? J Clin Diagn Res 10:Dc01–Dc03.  https://doi.org/10.7860/JCDR/2016/14989.7167 PubMedPubMedCentralGoogle Scholar
  42. Srinivasan VB, Rajamohan G, Gebreyes WA (2009) Role of AbeS, a novel efflux pump of the SMR family of transporters, in resistance to antimicrobial agents in Acinetobacter baumannii. Antimicrob Agents Chemother 53(12):5312–5316.  https://doi.org/10.1128/AAC.00748-09 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Su XZ, Chen J, Mizushima T, Kuroda T, Tsuchiya T (2005) AbeM, an H+-coupled Acinetobacter baumannii multidrug efflux pump belonging to the MATE family of transporters. Antimicrob Agents Chemother 49(10):4362–4364.  https://doi.org/10.1128/AAC.49.10.4362-4364.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Ultee A, Slump RA, Steging G, Smid EJ (2000) Antimicrobial activity of carvacrol toward Bacillus cereus on rice. J Food Prot 63(5):620–624.  https://doi.org/10.4315/0362-028X-63.5.620 CrossRefPubMedGoogle Scholar
  45. Wang Y (2002) The function of OmpA in Escherichia coli. Biochem Biophys Res Commun 292(2):396–401.  https://doi.org/10.1006/bbrc.2002.6657 CrossRefPubMedGoogle Scholar
  46. Wi YM, Choi JY, Lee JY, Kang CI, Chung DR, Peck KR, Song JH, Ko KS (2017) Antimicrobial effects of β-lactams on imipenem-resistant ceftazidime-susceptible Pseudomonas aeruginosa. Antimicrob Agents Chemother 61(6):e00054–e00017.  https://doi.org/10.1128/AAC.00054-17 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Wiest DB, Cochran JB, Tecklenburg FW (2012) Chloramphenicol toxicity revisited: a 12-year-old patient with a brain abscess. J Pediatr Pharmacol Ther 17(2):182–188.  https://doi.org/10.5863/1551-6776-17.2.182 PubMedPubMedCentralGoogle Scholar
  48. Wright GD (2016) Antibiotic adjuvants: rescuing antibiotics from resistance. Trends Microbiol 24(11):862–871.  https://doi.org/10.1016/j.tim.2016.06.009 CrossRefPubMedGoogle Scholar
  49. Yan N (2015) Structural biology of the major facilitator superfamily transporters. Annu Rev Biophys 44(1):257–283.  https://doi.org/10.1146/annurev-biophys-060414-033901 CrossRefPubMedGoogle Scholar
  50. Zhou F, Ji B, Zhang H, Jiang H, Yang Z, Li J, Yan W (2007) The antibacterial effect of cinnamaldehyde, thymol, carvacrol and their combinations against the food-borne pathogen Salmonella typhimurium. J Food Saf 27(2):124–133.  https://doi.org/10.1111/j.1745-4565.2007.00064.x CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Bora Shin
    • 1
  • Chulwoo Park
    • 1
  • James A. Imlay
    • 2
  • Woojun Park
    • 1
  1. 1.Laboratory of Molecular Environmental Microbiology, Department of Environmental Sciences and Ecological EngineeringKorea UniversitySeoulRepublic of Korea
  2. 2.Department of MicrobiologyUniversity of IllinoisUrbanaUSA

Personalised recommendations