1887

Abstract

Minocycline (MIN) and tigecycline (TIG) are antibiotics currently used for treatment of multidrug-resistant nosocomial pathogens. In this work, we show that blue light, as well as white light, modulates susceptibility to these antibiotics in a temperature-dependent manner. The modulation of susceptibility by light depends on the content of iron; an increase in iron results in a reduction in antibiotic susceptibility both under light and in the dark, though the effect is more pronounced in the latter condition. We further provide insights into the mechanism by showing that reduction in susceptibility to MIN and TIG induced by light is likely triggered by the generation of O, which, by a yet unknown mechanism, would ultimately lead to the activation of resistance genes such as those coding for the efflux pump AdeABC. The clinical relevance of these results may lie in surface-exposed wound infections, given the exposure to light in addition to the relatively low temperatures recorded in this type of lesion. We further show that the modulation of antibiotic susceptibility occurs not only in but also in other micro-organisms of clinical relevance such as and . Overall, our findings allow us to suggest that MIN and TIG antibiotic treatments may be improved by the inclusion of an iron chelator, in addition to keeping the wounds in the dark, a condition that would increase the effectiveness in the control of infections involving these micro-organisms.

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2015-05-01
2024-04-19
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References

  1. Avila-Pérez M., Hellingwerf K. J., Kort R. 2006; Blue light activates the σB-dependent stress response of Bacillus subtilis via YtvA. J Bacteriol 188:6411–6414 [View Article][PubMed]
    [Google Scholar]
  2. Berghoff B. A., Glaeser J., Sharma C. M., Vogel J., Klug G. 2009; Photooxidative stress-induced and abundant small RNAs in Rhodobacter sphaeroides . Mol Microbiol 74:1497–1512 [View Article][PubMed]
    [Google Scholar]
  3. Boucher H. W., Talbot G. H., Bradley J. S., Edwards J. E., Gilbert D., Rice L. B., Scheld M., Spellberg B., Bartlett J. 2009; Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 48:1–12 [View Article][PubMed]
    [Google Scholar]
  4. Boucher H. W., Talbot G. H., Benjamin D. K. Jr, Bradley J., Guidos R. J., Jones R. N., Murray B. E., Bonomo R. A., Gilbert D.Infectious Diseases Society of America 2013; 10×'20 Progress–development of new drugs active against gram-negative bacilli: an update from the Infectious Diseases Society of America. Clin Infect Dis 56:1685–1694 [View Article][PubMed]
    [Google Scholar]
  5. Bradford P. A., Weaver-Sands D. T., Petersen P. J. 2005; In vitro activity of tigecycline against isolates from patients enrolled in phase 3 clinical trials of treatment for complicated skin and skin-structure infections and complicated intra-abdominal infections. Clin Infect Dis 41:Suppl. 5S315–S332 [View Article][PubMed]
    [Google Scholar]
  6. Čikoš S., Bukovská A., Koppel J. 2007; Relative quantification of mRNA: comparison of methods currently used for real-time PCR data analysis. BMC Mol Biol 8:113 [View Article][PubMed]
    [Google Scholar]
  7. CLSI (2014). Performance Standards for Antimicrobial Susceptibility Testing; 24th Informational Supplement M100-S24. Wayne, PA: Clinical and Laboratory Standards Institute
  8. Galbis-Martínez M., Padmanabhan S., Murillo F. J., Elías-Arnanz M. 2012; CarF mediates signaling by singlet oxygen, generated via photoexcited protoporphyrin IX, in Myxococcus xanthus light-induced carotenogenesis. J Bacteriol 194:1427–1436 [View Article][PubMed]
    [Google Scholar]
  9. Golic A., Vaneechoutte M., Nemec A., Viale A. M., Actis L. A., Mussi M. A. 2013; Staring at the cold sun: blue light regulation is distributed within the genus Acinetobacter . PLoS ONE 8:e55059 [View Article][PubMed]
    [Google Scholar]
  10. Gomelsky M., Hoff W. D. 2011; Light helps bacteria make important lifestyle decisions. Trends Microbiol 19:441–448 [View Article][PubMed]
    [Google Scholar]
  11. Higgins P. G., Schneiders T., Hamprecht A., Seifert H. 2010; In vivo selection of a missense mutation in adeR and conversion of the novel blaOXA-164 gene into blaOXA-58 in carbapenem-resistant Acinetobacter baumannii isolates from a hospitalized patient. Antimicrob Agents Chemother 54:5021–5027 [View Article][PubMed]
    [Google Scholar]
  12. Hood M. I., Jacobs A. C., Sayood K., Dunman P. M., Skaar E. P. 2010; Acinetobacter baumannii increases tolerance to antibiotics in response to monovalent cations. Antimicrob Agents Chemother 54:1029–1041 [View Article][PubMed]
    [Google Scholar]
  13. Jung J., Baek J. H., Park W. 2010; Complete genome sequence of the diesel-degrading Acinetobacter sp. strain DR1. J Bacteriol 192:4794–4795 [View Article][PubMed]
    [Google Scholar]
  14. Karah N., Haldorsen B., Hegstad K., Simonsen G. S., Sundsfjord A., Samuelsen O.Norwegian Study Group of Acinetobacter 2011; Species identification and molecular characterization of Acinetobacter spp. blood culture isolates from Norway. J Antimicrob Chemother 66:738–744 [View Article][PubMed]
    [Google Scholar]
  15. Kochevar I. E., Redmond R. W. 2000; Photosensitized production of singlet oxygen. Methods Enzymol 319:20–28 [View Article][PubMed]
    [Google Scholar]
  16. Livak K. J., Schmittgen T. D. 2001; Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔ C T method. Methods 25:402–408 [View Article][PubMed]
    [Google Scholar]
  17. Lourenço R. F., Gomes S. L. 2009; The transcriptional response to cadmium, organic hydroperoxide, singlet oxygen and UV-A mediated by the σE–ChrR system in Caulobacter crescentus . Mol Microbiol 72:1159–1170 [View Article][PubMed]
    [Google Scholar]
  18. Máder K., Terhes G., Hajdú E., Urbán E., Sóki J., Magyar T., Márialigeti K., Katona M., Nagy E., Túri S. 2010; Outbreak of septicaemic cases caused by Acinetobacter ursingii in a neonatal intensive care unit. Int J Med Microbiol 300:338–340 [View Article][PubMed]
    [Google Scholar]
  19. Magiorakos A. P., Srinivasan A., Carey R. B., Carmeli Y., Falagas M. E., Giske C. G., Harbarth S., Hindler J. F., Kahlmeter G. et al. 2012; Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268–281 [View Article][PubMed]
    [Google Scholar]
  20. McGuiness W., Vella E., Harrison D. 2004; Influence of dressing changes on wound temperature. J Wound Care 13:383–385 [View Article][PubMed]
    [Google Scholar]
  21. Mellish K. J., Cox R. D., Vernon D. I., Griffiths J., Brown S. B. 2002; In vitro photodynamic activity of a series of methylene blue analogues. Photochem Photobiol 75:392–397 [View Article][PubMed]
    [Google Scholar]
  22. Mussi M. A., Gaddy J. A., Cabruja M., Arivett B. A., Viale A. M., Rasia R., Actis L. A. 2010; The opportunistic human pathogen Acinetobacter baumannii senses and responds to light. J Bacteriol 192:6336–6345 [View Article][PubMed]
    [Google Scholar]
  23. Mussi M. A., Limansky A. S., Relling V., Ravasi P., Arakaki A., Actis L. A., Viale A. M. 2011; Horizontal gene transfer and assortative recombination within the Acinetobacter baumannii clinical population provide genetic diversity at the single carO gene, encoding a major outer membrane protein channel. J Bacteriol 193:4736–4748 [View Article][PubMed]
    [Google Scholar]
  24. Oglesby-Sherrouse A. G., Djapgne L., Nguyen A. T., Vasil A. I., Vasil M. L. 2014; The complex interplay of iron, biofilm formation, and mucoidy affecting antimicrobial resistance of Pseudomonas aeruginosa . Pathog Dis 70:307–320 [View Article][PubMed]
    [Google Scholar]
  25. Ortiz-Guerrero J. M., Polanco M. C., Murillo F. J., Padmanabhan S., Elías-Arnanz M. 2011; Light-dependent gene regulation by a coenzyme B12-based photoreceptor. Proc Natl Acad Sci U S A 108:7565–7570 [View Article][PubMed]
    [Google Scholar]
  26. Penwell W. F., Arivett B. A., Actis L. A. 2012; The Acinetobacter baumannii entA gene located outside the acinetobactin cluster is critical for siderophore production, iron acquisition and virulence. PLoS ONE 7:e36493 [View Article][PubMed]
    [Google Scholar]
  27. Purcell E. B., Siegal-Gaskins D., Rawling D. C., Fiebig A., Crosson S. 2007; A photosensory two-component system regulates bacterial cell attachment. Proc Natl Acad Sci U S A 104:18241–18246 [View Article][PubMed]
    [Google Scholar]
  28. Ramírez M. S., Don M., Merkier A. K., Bistué A. J., Zorreguieta A., Centrón D., Tolmasky M. E. 2010; Naturally competent Acinetobacter baumannii clinical isolate as a convenient model for genetic studies. J Clin Microbiol 48:1488–1490 [View Article][PubMed]
    [Google Scholar]
  29. Ramírez M. S., Adams M. D., Bonomo R. A., Centrón D., Tolmasky M. E. 2011; Genomic analysis of Acinetobacter baumannii A118 by comparison of optical maps: identification of structures related to its susceptibility phenotype. Antimicrob Agents Chemother 55:1520–1526 [View Article][PubMed]
    [Google Scholar]
  30. Ribera A., Roca I., Ruiz J., Gibert I., Vila J. 2003; Partial characterization of a transposon containing the tet(A) determinant in a clinical isolate of Acinetobacter baumannii . J Antimicrob Chemother 52:477–480 [View Article][PubMed]
    [Google Scholar]
  31. Rice L. B. 2010; Progress and challenges in implementing the research on ESKAPE pathogens. Infect Control Hosp Epidemiol 31:Suppl. 1S7–S10 [View Article][PubMed]
    [Google Scholar]
  32. Rumbo C., Gato E., López M., Ruiz de Alegría C., Fernández-Cuenca F., Martínez-Martínez L., Vila J., Pachón J., Cisneros J. M. et al. 2013; Contribution of efflux pumps, porins, and β-lactamases to multidrug resistance in clinical isolates of Acinetobacter baumannii . Antimicrob Agents Chemother 57:5247–5257 [View Article][PubMed]
    [Google Scholar]
  33. Ruzin A., Keeney D., Bradford P. A. 2007; AdeABC multidrug efflux pump is associated with decreased susceptibility to tigecycline in Acinetobacter calcoaceticusAcinetobacter baumannii complex. J Antimicrob Chemother 59:1001–1004 [View Article][PubMed]
    [Google Scholar]
  34. Seifert H., Dijkshoorn L., Gerner-Smidt P., Pelzer N., Tjernberg I., Vaneechoutte M. 1997; Distribution of Acinetobacter species on human skin: comparison of phenotypic and genotypic identification methods. J Clin Microbiol 35:2819–2825[PubMed]
    [Google Scholar]
  35. Snitkin E. S., Zelazny A. M., Montero C. I., Stock F., Mijares L., Murray P. R., Segre J. A., Mullikin J., Blakesley R. et al. 2011; Genome-wide recombination drives diversification of epidemic strains of Acinetobacter baumannii . Proc Natl Acad Sci U S A 108:13758–13763 [View Article][PubMed]
    [Google Scholar]
  36. Sousa C., Silva L., Grosso F., Nemec A., Lopes J., Peixe L. 2014; Discrimination of the Acinetobacter calcoaceticusAcinetobacter baumannii complex species by Fourier transform infrared spectroscopy. Eur J Clin Microbiol Infect Dis 33:1345–1353 [View Article][PubMed]
    [Google Scholar]
  37. Swartz T. E., Tseng T. S., Frederickson M. A., Paris G., Comerci D. J., Rajashekara G., Kim J. G., Mudgett M. B., Splitter G. A. et al. 2007; Blue-light-activated histidine kinases: two-component sensors in bacteria. Science 317:1090–1093 [View Article][PubMed]
    [Google Scholar]
  38. Talbot G. H., Bradley J., Edwards J. E. Jr, Gilbert D., Scheld M., Bartlett J. G. 2006; Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin Infect Dis 42:657–668 [View Article][PubMed]
    [Google Scholar]
  39. Tan S. Y., Chua S. L., Liu Y., Høiby N., Andersen L. P., Givskov M., Song Z., Yang L. 2013; Comparative genomic analysis of rapid evolution of an extreme-drug-resistant Acinetobacter baumannii clone. Genome Biol Evol 5:807–818 [View Article][PubMed]
    [Google Scholar]
  40. Traglia G. M., Chua K., Centrón D., Tolmasky M. E., Ramírez M. S. 2014; Whole-genome sequence analysis of the naturally competent Acinetobacter baumannii clinical isolate A118. Genome Biol Evol 6:2235–2239 [View Article][PubMed]
    [Google Scholar]
  41. Turton J. F., Shah J., Ozongwu C., Pike R. 2010; Incidence of Acinetobacter species other than A. baumannii among clinical isolates of Acinetobacter: evidence for emerging species. J Clin Microbiol 48:1445–1449 [View Article][PubMed]
    [Google Scholar]
  42. Vilacoba E., Almuzara M., Gulone L., Traglia G. M., Figueroa S. A., Sly G., Fernández A., Centrón D., Ramírez M. S. 2013; Emergence and spread of plasmid-borne tet(B) : ISCR2 in minocycline-resistant Acinetobacter baumannii isolates. Antimicrob Agents Chemother 57:651–654 [View Article][PubMed]
    [Google Scholar]
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