There is an arising and concerning issue in the field of bacterial resistance, which is confirmed by the number of deaths associated with drug-resistant bacterial infections. The aim of this study was to compare the effects of antibiotics on Staphylococcus aureus non-resistant strain and strains resistant to cadmium or lead ions. Metal resistant strains were created by the gradual addition of 2 mM solution of metal ions (cadmium or lead) to the S. aureus culture. An increasing antimicrobial effect of ampicillin, streptomycin, penicillin and tetracycline (0, 10, 25, 50, 75, 150, 225 and 300 µM) on the resistant strains was observed using a method of growth curves. A significant growth inhibition (compared to control) of cadmium resistant cells was observed in the presence of all the four different antibiotics. On the other hand, the addition of streptomycin and ampicillin did not inhibit the growth of lead resistant strain. Other antibiotics were still toxic to the bacterial cells. Significant differences in the morphology of cell walls were indicated by changes in the cell shape. Our data show that the presence of metal ions in the urban environment may contribute to the development of bacterial strain resistance to other substances including antibiotics, which would have an impact on public health.

Central European Institute of Technology Brno University of Technology Technicka 3058 10 Brno CZ 616 00 Czech Republic

Department of Chemistry and Biochemistry Faculty of Agronomy Mendel University in Brno Zemedelska 1 Brno CZ 613 00 Czech Republic

Karel Englis College Sujanovo nam 356 1 Brno CZ 602 00 Czech Republic

Zobrazit více v PubMed

Levy S.B., Marshall B. Antibacterial resistance worldwide: Causes, challenges and responses. Nat. Med. 2004;10:S122–S129. doi: 10.1038/nm1145. PubMed DOI

Zhou F., Wang Y. Characteristics of antibiotic resistance of airborne Staphylococcus isolated from metro stations. Int. J. Environ. Res. Public Health. 2013;10:2412–2426. doi: 10.3390/ijerph10062412. PubMed DOI PMC

Gatica J., Cytryn E. Impact of treated wastewater irrigation on antibiotic resistance in the soil microbiome. Environ. Sci. Pollut. Res. 2013;20:3529–3538. doi: 10.1007/s11356-013-1505-4. PubMed DOI PMC

Stone N.D., Lewis D.R., Lowery H.K., Darrow L.A., Kroll C.M., Gaynes R.P., Jernigan J.A., McGowan J.E., Tenover F.C., Richards C.L. Importance of bacterial burden among methicillin-resistant Staphylococcus aureus carriers in a long-term care facility. Infect. Control Hosp. Epidemiol. 2008;29:143–148. doi: 10.1086/526437. PubMed DOI

Bastug A., Yilmaz G.R., Kayaaslan B., Akinci E., Bodur H. Risk factors for mortality in patients with nosocomial Staphylococcus aureus bacteremia. Turk. J. Med. Sci. 2012;42:1222–1229.

Tacconelli E., Pop-Vicas A.E., D’Agata E.M.C. Increased mortality among elderly patients with meticillin-resistant Staphylococcus aureus bacteraemia. J. Hosp. Infect. 2006;64:251–256. doi: 10.1016/j.jhin.2006.07.001. PubMed DOI

Cosgrove S.E., Qi Y.L., Kaye K.S., Harbarth S., Karchmer A.W., Carmeli Y. The impact of methicillin-resistance in Staphylococcus aureus bacteremia on patient outcomes: Mortality, length of stay, and hospital charges. Infect. Control Hosp. Epidemiol. 2005;26:166–174. PubMed

Ammerlaan H.S.M., Harbarth S., Buiting A.G.M., Crook D.W., Fitzpatrick F., Hanberger H., Herwaldt L.A., van Keulen P.H.J., Kluytmans J., Kola A., et al. Secular trends in nosocomial bloodstream infections: Antibiotic-resistant bacteria increase the total burden of infection. Clin. Infect. Dis. 2013;56:798–805. doi: 10.1093/cid/cis1006. PubMed DOI

Ye Y., Li S.L., Li Y.J., Ren T.S., Liu K.G. Mycoplasma pneumoniae 23S rRNA Gene Mutations and Mechanisms of Macrolide Resistance. Labmedicine. 2013;44:63–68.

Aktan Y., Tan S., Icgen B. Characterization of lead-resistant river isolate Enterococcus faecalis and assessment of its multiple metal and antibiotic resistance. Environ. Monit. Assess. 2013;185:5285–5293. doi: 10.1007/s10661-012-2945-x. PubMed DOI

Hellweger F.L. Simple model of tetracycline antibiotic resistance in aquatic environment: Accounting for metal coselection. J. Environ. Eng.-ASCE. 2013;139:913–921. doi: 10.1061/(ASCE)EE.1943-7870.0000696. DOI

My N.H., Hirao H., Van D.U., Morokuma K. Computational studies of bacterial resistance to beta-lactam antibiotics: Mechanism of covalent inhibition of the penicillin-binding protein 2a (PBP2a) J. Chem. Inf. Model. 2011;51:3226–3234. doi: 10.1021/ci2004175. PubMed DOI

Yuan W.C., Hu Q.W., Cheng H., Shang W.L., Liu N., Hua Z.Y., Zhu J.M., Hu Z., Yuan J.Z., Zhang X., et al. Cell wall thickening is associated with adaptive resistance to amikacin in methicillin-resistant Staphylococcus aureus clinical isolates. J. Antimicrob. Chemother. 2013;68:1089–1096. doi: 10.1093/jac/dks522. PubMed DOI

Anaya-Lopez J.L., Lopez-Meza J.E., Ochoa-Zarzosa A. Bacterial resistance to cationic antimicrobial peptides. Crit. Rev. Microbiol. 2013;39:180–195. doi: 10.3109/1040841X.2012.699025. PubMed DOI

Majzlik P., Strasky A., Adam V., Nemec M., Trnkova L., Zehnalek J., Hubalek J., Provaznik I., Kizek R. Influence of zinc(II) and copper(II) ions on Streptomyces bacteria revealed by electrochemistry. Int. J. Electrochem. Sci. 2011;6:2171–2191.

Sobrova P., Zehnalek J., Adam V., Beklova M., Kizek R. The effects on soil/water/plant/animal systems by platinum group elements. Cent. Eur. J. Chem. 2012;10:1369–1382. doi: 10.2478/s11532-012-0073-7. DOI

Krizkova S., Huska D., Beklova M., Hubalek J., Adam V., Trnkova L., Kizek R. Protein-based electrochemical biosensor for detection of silver(I) ions. Environ. Toxicol. Chem. 2010;29:492–496. doi: 10.1002/etc.77. PubMed DOI

Pereira P.M., Filipe S.R., Tomasz A., Pinho M.G. Fluorescence ratio imaging microscopy shows decreased access of vancomycin to cell wall synthetic sites in vancomycin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 2007;51:3627–3633. doi: 10.1128/AAC.00431-07. PubMed DOI PMC

Summers A.O. Genetic linkage and horizontal gene transfer, the roots of the antibiotic multi-resistance problem. Anim. Biotechnol. 2006;17:125–135. doi: 10.1080/10495390600957217. PubMed DOI

Resende J.A., Silva V.L., Fontes C.O., Souza J.A., de Oliveira T.L.R., Coelho C.M., Cesar D.E., Diniz C.G. Multidrug-resistance and toxic metal tolerance of medically important bacteria isolated from an aquaculture system. Microbes Environ. 2012;27:449–455. doi: 10.1264/jsme2.ME12049. PubMed DOI PMC

Ji X.L., Shen Q.H., Liu F., Ma J., Xu G., Wang Y.L., Wu M.H. Antibiotic resistance gene abundances associated with antibiotics and heavy metals in animal manures and agricultural soils adjacent to feedlots in Shanghai, China. J. Hazard. Mater. 2012;235:178–185. PubMed

Malik A., Aleem A. Incidence of metal and antibiotic resistance in Pseudomonas spp. from the river water, agricultural soil irrigated with wastewater and groundwater. Environ. Monit. Assess. 2011;178:293–308. doi: 10.1007/s10661-010-1690-2. PubMed DOI

Adam V., Fabrik I., Kohoutkova V., Babula P., Hubalek J., Vrba R., Trnkova L., Kizek R. Automated electrochemical analyzer as a new tool for detection of thiols. Int. J. Electrochem. Sci. 2010;5:429–447.

Adam V., Baloun J., Fabrik I., Trnkova L., Kizek R. An electrochemical detection of metallothioneins at the zeptomole level in nanolitre volumes. Sensors. 2008;8:2293–2305. doi: 10.3390/s8042293. PubMed DOI PMC

Adam V., Blastik O., Krizkova S., Lubal P., Kukacka J., Prusa R., Kizek R. Application of the Brdicka reaction in determination of metallothionein in patients with tumours. Chem. Listy. 2008;102:51–58.

Maret W. Fluorescent probes for the structure and function of metallothionein. J. Chromatogr. B. 2009;877:3378–3383. doi: 10.1016/j.jchromb.2009.06.014. PubMed DOI

Sobrova P., Vyslouzilova L., Stepankova O., Ryvolova M., Anyz J., Trnkova L., Adam V., Hubalek J., Kizek R. Tissue specific electrochemical fingerprinting. PLoS One. 2012;7:e49654. doi: 10.1371/journal.pone.0049654. PubMed DOI PMC

Brissonnoel A., Trieucuot P., Courvalin P. Mechanisms of action of spiramycin and other macrolides. J. Antimicrob. Chemother. 1988;22:13–23. PubMed

Jenkins R., Burton N., Cooper R. Manuka honey inhibits cell division in methicillin-resistant Staphylococcus aureus. J. Antimicrob. Chemother. 2011;66:2536–2542. doi: 10.1093/jac/dkr340. PubMed DOI

Belley A., Harris R., Beveridge T., Parr T., Moeck G. Ultrastructural effects of oritavancin on methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Antimicrob. Agents Chemother. 2009;53:800–804. doi: 10.1128/AAC.00603-08. PubMed DOI PMC

Webster D., Rennie R.P., Brosnikoff C.L., Chui L., Brown C. Methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in Canada. Diagn. Microbiol. Infect. Dis. 2007;57:177–181. doi: 10.1016/j.diagmicrobio.2006.07.007. PubMed DOI

Rouch D.A., Lee B.T.O., Morby A.P. Understanding cellular-responses to toxic agents—A model for mechanism-choice in bacterial metal resistance. J. Ind. Microbiol. 1995;14:132–141. doi: 10.1007/BF01569895. PubMed DOI

Trajanovska S., Britz M.L., Bhave M. Detection of heavy metal ion resistance genes in Gram-positive and Gram-negative bacteria isolated from a lead-contaminated site. Biodegradation. 1997;8:113–124. doi: 10.1023/A:1008212614677. PubMed DOI

Nies D.H., Silver S. Ion efflux systems involved in bacterial metal resistances. J. Ind. Microbiol. 1995;14:186–199. doi: 10.1007/BF01569902. PubMed DOI

Nies D.H. Microbial heavy-metal resistance. Appl. Microbiol. Biotechnol. 1999;51:730–750. doi: 10.1007/s002530051457. PubMed DOI

Choudhury R., Srivastava S. Zinc resistance mechanisms in bacteria. Curr. Sci. 2001;81:768–775.

Naik M.M., Dubey S.K., Khanolkar D., D’Costa B. P-type ATPase and MdrL efflux pump-mediated lead and multi-drug resistence in estuarine bacterial isolates. Curr. Sci. 2013;105:1366–1372.

Blaszak M., Bienkowska D. Effect of soil pollution on bacterial resistance to lead ions: An experimental approach. Pol. J. Ecol. 2009;57:555–560.

Rensing C., Sun Y., Mitra B., Rosen B.P. Pb(II)-translocating P-type ATPases. J. Biol. Chem. 1998;273:32614–32617. doi: 10.1074/jbc.273.49.32614. PubMed DOI

Levinson H.S., Mahler I., Blackwelder P., Hood T. Lead resistance and sensitivity in Staphylococcus aureus. FEMS Microbiol. Lett. 1996;145:421–425. doi: 10.1111/j.1574-6968.1996.tb08610.x. PubMed DOI

Deb S., Ahmed S.F., Basu M. Metal accumulation in cell wall: A possible mechanism of cadmium resistance by Pseudomonas stutzeri. Bull. Environ. Contam. Toxicol. 2013;90:323–328. doi: 10.1007/s00128-012-0933-z. PubMed DOI

Baker-Austin C., Wright M.S., Stepanauskas R., McArthur J.V. Co-selection of antibiotic and metal resistance. Trends Microbiol. 2006;14:176–182. doi: 10.1016/j.tim.2006.02.006. PubMed DOI

Chapman J.S. Disinfectant resistance mechanisms, cross-resistance, and co-resistance. Int. Biodeterior. Biodegrad. 2003;51:271–276. doi: 10.1016/S0964-8305(03)00044-1. DOI

Jensen S.O., Kwong S.M., Lyon B.R., Firth N. Evolution of multiple drug resistance in Staphylococci. Microbiol. Aust. 2008;29:120–123.

Jensen S.O., Lyon B.R. Genetics of antimicrobial resistance in Staphylococcus aureus. Future Microbiol. 2009;4:565–582. PubMed

Novick R.P., Roth C. Plasmid-linked resistance to inorganic salts in Staphylococcus aureus. J. Bacteriol. 1968;95:1335–1342. PubMed PMC

Chopra I., Roberts M. Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol. Mol. Biol. Rev. 2001;65:232–260. doi: 10.1128/MMBR.65.2.232-260.2001. PubMed DOI PMC

Lacey R.W., Chopra I. Evidence for mutation to streptomycin resistance in clinical strains of Staphylococcus aureus. J. Gen. Microbiol. 1972;73:175–180. doi: 10.1099/00221287-73-1-175. PubMed DOI

Derbise A., de Cespedes G., el Solh N. Nucleotide sequence of the Staphylococcus aureus transposon, Tn5405, carrying aminoglycosides resistance genes. J. Basic Microbiol. 1997;37:379–384. doi: 10.1002/jobm.3620370511. PubMed DOI

Singh V.K., Xiong A.M., Usgaard T.R., Chakrabarti S., Deora R., Misra T.K., Jayaswal R.K. ZntR is an autoregulatory protein and negatively regulates the chromosomal zinc resistance operon znt of Staphylococcus aureus. Mol. Microbiol. 1999;33:200–207. doi: 10.1046/j.1365-2958.1999.01466.x. PubMed DOI

Yoon K.P., Misra T.K., Silver S. Regulation of the cadA cadmium resistance determinant of Staphylococcus aureus plasmid PI258. J. Bacteriol. 1991;173:7643–7649. PubMed PMC

Yoon K.P., Silver S. A 2nd gene in the Staphylococcus aureus cadA cadmium resistance determinant of plasmid-PI258. J. Bacteriol. 1991;173:7636–7642. PubMed PMC

Okkeri J., Haltia T. Expression and mutagenesis of ZntA, a zinc-transporting P-type ATPase from Escherichia coli. Biochemistry. 1999;38:14109–14116. doi: 10.1021/bi9913956. PubMed DOI

Stomeo F., Valverde A., Pointing S.B., McKay C.P., Warren-Rhodes K.A., Tuffin M.I., Seely M., Cowan D.A. Hypolithic and soil microbial community assembly along an aridity gradient in the Namib Desert. Extremophiles. 2013;17:329–337. doi: 10.1007/s00792-013-0519-7. PubMed DOI

Xiong A.M., Jayaswal R.K. Molecular characterization of a chromosomal determinant conferring resistance to zinc and cobalt ions in Staphylococcus aureus. J. Bacteriol. 1998;180:4024–4029. PubMed PMC

Thelwell C., Robinson N.J., Turner-Cavet J.S. An SmtB-like repressor from Synechocystis PCC 6803 regulates a zinc exporter. Proc. Natl. Acad. Sci. USA. 1998;95:10728–10733. doi: 10.1073/pnas.95.18.10728. PubMed DOI PMC

Cook W.J., Kar S.R., Taylor K.B., Hall L.M. Crystal structure of the cyanobacterial metallothionein repressor SmtB: A model for metalloregulatory proteins. J. Mol. Biol. 1998;275:337–346. doi: 10.1006/jmbi.1997.1443. PubMed DOI

Shi W.P., Dong J., Scott R.A., Ksenzenko M.Y., Rosen B.P. The role of arsenic thiol interactions in metalloregulation of the ars operon. J. Biol. Chem. 1996;271:9291–9297. PubMed

Prusa R., Kizek R., Trnkova L., Vacek J., Zehnalek J. Study of relationship between metallothionein and heavy metals by CPSA method. Clin. Chem. 2004;50:A28–A29.

Vasak M. Advances in metallothionein structure and functions. J. Trace Elem. Med. Biol. 2005;19:13–17. doi: 10.1016/j.jtemb.2005.03.003. PubMed DOI

Skalickova S., Zitka O., Nejdl L., Krizkova S., Sochor J., Janu L., Ryvolova M., Hynek D., Zidkova J., Zidek V., et al. Study of interaction between metallothionein and CdTe quantum dots. Chromatographia. 2013;76:345–353. doi: 10.1007/s10337-013-2418-6. DOI

Huckle J.W., Morby A.P., Turner J.S., Robinson N.J. Isolation of a prokaryotic metallothionein locus and analysis of transcriptional control by trace-metal ions. Mol. Microbiol. 1993;7:177–187. doi: 10.1111/j.1365-2958.1993.tb01109.x. PubMed DOI

Klaassen C.D., Liu J., Diwan B.A. Metallothionein protection of cadmium toxicity. Toxicol. Appl. Pharmacol. 2009;238:215–220. doi: 10.1016/j.taap.2009.03.026. PubMed DOI PMC

Templeton D.M., Cherian M.G. Toxicological significance of metallothionein. Method Enzymol. 1991;205:11–24. doi: 10.1016/0076-6879(91)05079-B. PubMed DOI

Sochor J., Pohanka M., Ruttkay-Nedecky B., Zitka O., Hynek D., Mares P., Zeman L., Adam V., Kizek R. Effect of selenium in organic and inorganic form on liver, kidney, brain and muscle of Wistar rats. Cent. Eur. J. Chem. 2012;10:1442–1451. doi: 10.2478/s11532-012-0064-8. DOI

Coyle P., Philcox J.C., Carey L.C., Rofe A.M. Metallothionein: The multipurpose protein. Cell. Mol. Life Sci. 2002;59:627–647. doi: 10.1007/s00018-002-8454-2. PubMed DOI PMC

Henkel G., Krebs B. Metallothioneins: Zinc, cadmium, mercury, and copper thiolates and selenolates mimicking protein active site features—Structural aspects and biological implications. Chem. Rev. 2004;104:801–824. doi: 10.1021/cr020620d. PubMed DOI

Adam V., Fabrik I., Eckschlager T., Stiborova M., Trnkova L., Kizek R. Vertebrate metallothioneins as target molecules for analytical techniques. TRAC-Trends Anal. Chem. 2010;29:409–418. doi: 10.1016/j.trac.2010.02.004. DOI

Krizkova S., Ryvolova M., Hrabeta J., Adam V., Stiborova M., Eckschlager T., Kizek R. Metallothioneins and zinc in cancer diagnosis and therapy. Drug Metab. Rev. 2012;44:287–301. doi: 10.3109/03602532.2012.725414. PubMed DOI

Naik M.M., Shamim K., Dubey S.K. Biological characterization of lead-resistant bacteria to explore role of bacterial metallothionein in lead resistance. Curr. Sci. 2012;103:426–429.

Platinum nanoparticles induce damage to DNA and inhibit DNA replication

Influence of microbiome species in hard-to-heal wounds on disease severity and treatment duration