Negative correlation between virulence and multidrug resistance in intrahospital and community acquired infections by Proteus mirabilis, in Eastern Venezuela.
Correlación negativa entre la viruluencia y la resistencia multidroga en infecciones intrahospitalarias y adquiridas en la comunidad por Proteus mirabilis, en el Oriente de Venezuela
Keywords:
Proteus, MDR, virulence, resistance, antimicrobials
Abstract
This is thefirst report for Venezuela of virulence/pathogenicity and resistance factors in intrahospital (HCAI) and community-acquired infec-tions (CAI) by P. mirabilis in two main hospitals from Eastern Venezuela. Viru-lence factors such as motility, biofilms, and resistance to serum killing (RSK) were determined. Antimicrobial susceptibility allowed classifying the isolates into resistant, multidrug resistant (MDR) and extensively drug-resistant (XDR). P. mirabilis was identified in HCAI in both hospitals mostly from secretions, while some CAI were identified from urine and secretions. Twitching, swarm-ing, biofilm and RSK were identified in many isolates. Eleven antimicrobials showed resistance frequencies from 22-54% in one or both hospitals. A high frequency of MDR isolates was found in these hospitals (60.6 to 56.5%). Strains carrying both blaCTX-M and blaTEM genes were found in one hospital in a frequency of 27.0%. We also found that the frequency of MDR was lower in strains with three or more virulence factors compared to those with fewer factors. Bacteria with swarming showed 5.85 times lower probability of being MDR, and those with twitching, 7.52 times lower probability. Infections by MDR/XDR P. mira-bilis strains in HCAI and CAI represent a public health problem that requires effective control and prevention measures to reduce their potential spread and persistence in the population
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References
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Edelstein M, Pimkin M, Palagin I, Edelstein I, Stratchounski L. Prevalence and molecular epidemiology of CTX-M extended spectrum betalactamase producing Escherichia coli and Klebsiella pneumoniae in Russian hospitals. Antimicrob Agents Chemother 2003; 47(12):3724-3732. https:// doi. org/10.1128/aac.47.12.3724-3732.2003.
Alabi OS, Mendonça N, Adeleke OE, da Silva GJ. Molecular screening of antibiotic- resistant determinants among multidrug-resistant clinical isolates of Proteus mirabilis from SouthWest Nigeria. Afri Health Sci 2017; 17(2), 356-365. https://doi. org/10.4314/ahs.v17i2.9
Miryala SK, Anbarasu A, Ramaiah S. Gene interaction network approach to elucidate the multidrug resistance mechanisms in the pathogenic bacterial strain Proteus mirabilis. J Cel Physiol 2021; 236: 468-479 https://doi.org/10.1002/jcp.29874.
El Mekes A, Zahlane K, Ait Said L, Tadlaoui Ouafi A, Barakate M. The clinical and epidemiological risk factors of infec- tions due to multi-drug resistant bacteria in an adult intensive care unit of University Hospital Center in Marrakesh-Morocco. J Infect Public Health 2019; 13(4):637-643. https://doi.org/10.1016/j.jiph.2019.08.012
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Custovic A, Smajlovic J, Hadzic S, Ahmetagic S, Tihic N, Hadzagic H. Epidemiological surveillance of bacterial nosocomial infections in the surgical intensive care unit. Mater Sociomed 2014; 26(1):7-11. https:// doi.org/10.5455/msm.2014.26.7-11.
Matsuyama T, Takagi Y, Nakagawa Y, Itoh H, Wakita J, Matsushita M. Dynamic aspects of the structured cell population in swarming colony of Proteus mirabilis. J Bacteriol 2000; 182:385-393. https://doi. org/10.1128/jb.182.2.385-393.2000.
Morgenstein RM, Szostek B, Rather PN. Regulation of gene expression during swarmer cell diferentiation in Proteus mirabilis. FEMS Microbiol Rev 2010; 34:753-763. https://doi. org/10.1111/j.1574-6976. 2010.00229.x
Zunino P, Piccini C, Legnani-Fajardo C. Flagellate and non-flagellate Proteus mirabilis in the development of experimental urinary tract infection. Microb Pathog 1994; 16:379-385. https://doi.org/10.1006/mp at.1994.1038
Legnani-Fajardo C, Zunino P, Piccini C, Allen A, Maskell D. Defined mutants of Proteus mirabilis lacking flagella cause ascending urinary tract infection in mice. Microb Pathog 1996; 21:395-405. https://doi. org/10.1006/mpat.1996.0070.
Armbruster CE, Mobley HL, Pearson MM. Pathogenesis of Proteus mirabilis infection. EcoSal Plus 2018; 8(1):10.1128/ecosalplus. ESP-0009-2017. https://doi.org/10.1128/ ecosalplus.ESP-0009-2017.
O’Toole GA, Kolter R. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol Microbiol 1998; 30(2):295-304. https://doi. org/10.1046/j.1365-2958.1998.01062.x.
Belas R. When the swimming gets tough the tough form a biofilm. Mol Microbiol 2013; 90(1):1-5. https://doi.org/10.1111/ mmi.12354
Smith AW. Biofilms and antibiotic therapy: is there a role for combating bacterial resistance by the use of novel drug delivery systems? Adv Drug Deliv Rev 2005; 57(10):1539-1550. https://doi.org/10.1016/j.addr.2005.04.007
Thiriard A, Raze D, Locht C. Diversion of complement-mediated killing by Bordetella. Microbes Infect 2018; 20(9-10):512-520. https://doi.org/10.1016/j.mi- cinf.2018.02.002.
Moffatt J, Harper M, Boyce J. Mechanisms of Polymyxin Resistance. In: Li J., Nation R., Kaye K. (eds) Polymyxin Antibiotics: From Laboratory Bench to Bedside. Advances in Experimental Medicine and Biology, vol 1145. Springer, Cham. 2019. https://doi. org/10.1007/978-3-030-16373-0_5.
Castanheira M, Deshpande LM, Mendes RE, Canton R, Sader HS, Jones RN. Variations in the occurrence of resistance phenotypes and carbapenemase genes among Enterobacteriaceae isolates in 20 Years of the SENTRY Antimicrobial Surveillance Program. Open Forum Infect Dis 2019; 15(Suppl. 1):S23-S33. https://doi. org/10.1093/ofid/ofy347.
Bou G. Relación entre resistencia y virulencia en bacterias de interés clínico. Enferm Infecc Microbiol Clin 2014; 32(1):1-3. https://doi.org/10.1016/j.eimc.2013.11.002.
Beceiro A, Tomás M, Bou G. Antimicrobial resistance and virulence: a successful or deleterious association in the bacterial world? Clin Microbiol Rev 2013; 26(2):185-230. https://doi.org/10.1128/CMR.00059-12.
Chouduri A, Wadud A, Islam A. Extended spectrum multi-drug resistance versus pathogenic factors- swarming, proteases, and urease-of Proteus species. Int Res J Microbiol 2014; 5(1):8-15. https://doi.org/ 10.14303/irjm.2013.052.
Armbruster CE, Mobley HL. Merging mythology and morphology: the multifaceted lifestyle of Proteus mirabilis. Nat Rev Microbiol 2012; 10:743-754. https://doi. org/10.1038/nrmicro2890.
Jacobsen SM, Shirtliff ME. Proteus mirabilis biofilms and catheter-associated urinary tract infections. Virulence 2011; 2:460-465. https://doi.org/ 10.4161/viru.2.5.17783.
Stock I. Natural antibiotic susceptibility of Proteus spp., with special reference to P. mirabilis and P. penneri strains. J Chemother 2003; 15:12-26. https://doi.org/10.1179/ joc.2003.15.1.12.
Sader HS, Farrell DJ, Flamm RK, Jones RN. Antimicrobial susceptibility of Gram negative organisms isolated from patients hospitalized in intensive care units in United States and European hospitals (2009- 2011). Diagn Microbiol Infect Dis 2014; 78:443-448. https://doi.org/10.1016/j.diag microbio.2013.11.025
Bedenić B, Firis N, Elveđi-Gašparović V, Krilanović M, Matanović K, Štimac I, Luxner J, Vraneš J, Meštrović T, Zarfel G, Grisold A. Emergence of multidrug-resistant Proteus mirabilis in a long-term care facility in Croatia. Wien Klin Wochenschr 2016; 128:404-413. https://doi.org/10.1007/s00 508-016-1005-x
Bonnet R, Sampaio JL, Labia R, Champs C, Sirot D, Chanel C, Sirot J. A novel CTX- M β-lactamases (CTX-M-8) in cefotaxime-resistant Enterobacteriaceae isolated in Brazil. Antimicrob Agents Chemother 2004; 44:1936-1942. https://doi.org/10.1128/ aac.44.7.1936-1942.2000
Casabonne C, Pérez J, Balagué C, Fernández L. Diversidad de β-lactamasas en aislamientos clínicos de enterobacterias. Acta Bioquim Clin Latinoam 2012; 46(3):405-412.
Miranda J, Pinto J, Faustino M, Sánchez-Jacinto B, Ramírez F. Antimicrobial resistance of uropathogens in older adults in a private clinic in Lima, Peru. Rev Peru Med Exp Salud Publica 2019; 36(1):87-92. https://doi.org/10.17843/rp- mesp.2019.361.3765.
Cardoso T, Almeida M, Friedman ND, Aragao I, Costa-Pereira A, Sarmento A, Azevedo L. Classification of healthcare-associated infection: a systematic review 10 years after the first proposal. BMC Med 2014; 12:40. https:// doi.org/10.1186/1741-7015-12-40.
Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas M, Giske C, Harbarth S, Hindler J, Kahlmeter G, Olsson- Liljequist B, Paterson D, Rice L, Stelling J, Struelens M, Vatopoulos A, Weber J, Monnet D. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18(3):268-281. https://doi.org/10.1111/ j.1469-0691.2011.03570.x
Kwiecinska-Piróg J, Bogiel T, Skowron K, Wieckowska E, Gospodarek E. Proteus mirabilis biofilm-qualitative and quantitative colorimetric methods-based evaluation. Braz J Microbiol 2014; 45(4), 1423-1431. https://doi.org/10.1590/S1517-83822014000400037
Hola V, Peroutkova T, Ruzicka F. Virulence factors in Proteus bacteria from biofilm communities of catheter-associated urinary tract infections. FEMS Immunol Med Microbiol 2012; 65:343-349. https://doi. org/10.1111/j.1574-695X.2012.00976.x
Kwil I, Kaźmierczak D, Różalski A. Swarming growth and resistance of Proteus penneri and Proteus vulgaris strains to normal human serum. Adv Clin Exp Med 2013; 22(2):165-175.
CLSI. Performance Standards for Antimicrobial Susceptibility Testing, 30th Ed. CLSI supplement M100. Wayne, PA, USA. Clinical and Laboratory Standards Institute, 2020.
Poulou A, Grivakou E, Vrioni G, Koumaki V, Pittaras T, Pournaras S, Tsakris A. Modified CLSI extended-spectrum β-lactamase (ESBL) confirmatory test for phenotypic detection of ESBLs among Enterobacteriaceae producing various β-lactamases. J Clin Microbiol 2014; 52(5):1483-1489. https:// doi.org/10.1128/JCM.03361-13.
Galani I, Xirouchaki E, Kanellakopoulou K, Petrikkos G, Giamarellou H. Transferable plasmid mediating resistance to multiple antimicrobial agents in Klebsiella pneumoniae isolates in Greece. Clin Microbiol Infect 2002; 8:579-588. https://doi. org/10.1046/j.1469-0691.2002.00391.x.
Aarestrup FM, Lertworapreecha M, Evans MC, Bangtrakulnonth A, Chalermchaikit T, Hendriksen R, Wegener H. Antimicrobial susceptibility and occurrence of resistance genes among Salmonella enterica serovar Weltevreden from different countries. J Antimicrob Chemother 2003; 52:715-718. https://doi.org/10.1093/jac/dkg426.
Edelstein M, Pimkin M, Palagin I, Edelstein I, Stratchounski L. Prevalence and molecular epidemiology of CTX-M extended spectrum betalactamase producing Escherichia coli and Klebsiella pneumoniae in Russian hospitals. Antimicrob Agents Chemother 2003; 47(12):3724-3732. https:// doi. org/10.1128/aac.47.12.3724-3732.2003.
Alabi OS, Mendonça N, Adeleke OE, da Silva GJ. Molecular screening of antibiotic- resistant determinants among multidrug-resistant clinical isolates of Proteus mirabilis from SouthWest Nigeria. Afri Health Sci 2017; 17(2), 356-365. https://doi. org/10.4314/ahs.v17i2.9
Miryala SK, Anbarasu A, Ramaiah S. Gene interaction network approach to elucidate the multidrug resistance mechanisms in the pathogenic bacterial strain Proteus mirabilis. J Cel Physiol 2021; 236: 468-479 https://doi.org/10.1002/jcp.29874.
El Mekes A, Zahlane K, Ait Said L, Tadlaoui Ouafi A, Barakate M. The clinical and epidemiological risk factors of infec- tions due to multi-drug resistant bacteria in an adult intensive care unit of University Hospital Center in Marrakesh-Morocco. J Infect Public Health 2019; 13(4):637-643. https://doi.org/10.1016/j.jiph.2019.08.012
Feglo P, Gbedema S, Quay S, Adu-Sarkodie Y, Opoku-Okrah C. Occurrence, species distribution and antibiotic resistance of Proteus isolates: A case study at the Komfo Anokye Teaching Hospital (KATH) in Ghana. Int J Pharma Sci Res 2010; 1:347-352.
Custovic A, Smajlovic J, Hadzic S, Ahmetagic S, Tihic N, Hadzagic H. Epidemiological surveillance of bacterial nosocomial infections in the surgical intensive care unit. Mater Sociomed 2014; 26(1):7-11. https:// doi.org/10.5455/msm.2014.26.7-11.
Matsuyama T, Takagi Y, Nakagawa Y, Itoh H, Wakita J, Matsushita M. Dynamic aspects of the structured cell population in swarming colony of Proteus mirabilis. J Bacteriol 2000; 182:385-393. https://doi. org/10.1128/jb.182.2.385-393.2000.
Morgenstein RM, Szostek B, Rather PN. Regulation of gene expression during swarmer cell diferentiation in Proteus mirabilis. FEMS Microbiol Rev 2010; 34:753-763. https://doi. org/10.1111/j.1574-6976. 2010.00229.x
Zunino P, Piccini C, Legnani-Fajardo C. Flagellate and non-flagellate Proteus mirabilis in the development of experimental urinary tract infection. Microb Pathog 1994; 16:379-385. https://doi.org/10.1006/mp at.1994.1038
Legnani-Fajardo C, Zunino P, Piccini C, Allen A, Maskell D. Defined mutants of Proteus mirabilis lacking flagella cause ascending urinary tract infection in mice. Microb Pathog 1996; 21:395-405. https://doi. org/10.1006/mpat.1996.0070.
Armbruster CE, Mobley HL, Pearson MM. Pathogenesis of Proteus mirabilis infection. EcoSal Plus 2018; 8(1):10.1128/ecosalplus. ESP-0009-2017. https://doi.org/10.1128/ ecosalplus.ESP-0009-2017.
O’Toole GA, Kolter R. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Mol Microbiol 1998; 30(2):295-304. https://doi. org/10.1046/j.1365-2958.1998.01062.x.
Belas R. When the swimming gets tough the tough form a biofilm. Mol Microbiol 2013; 90(1):1-5. https://doi.org/10.1111/ mmi.12354
Smith AW. Biofilms and antibiotic therapy: is there a role for combating bacterial resistance by the use of novel drug delivery systems? Adv Drug Deliv Rev 2005; 57(10):1539-1550. https://doi.org/10.1016/j.addr.2005.04.007
Thiriard A, Raze D, Locht C. Diversion of complement-mediated killing by Bordetella. Microbes Infect 2018; 20(9-10):512-520. https://doi.org/10.1016/j.mi- cinf.2018.02.002.
Moffatt J, Harper M, Boyce J. Mechanisms of Polymyxin Resistance. In: Li J., Nation R., Kaye K. (eds) Polymyxin Antibiotics: From Laboratory Bench to Bedside. Advances in Experimental Medicine and Biology, vol 1145. Springer, Cham. 2019. https://doi. org/10.1007/978-3-030-16373-0_5.
Castanheira M, Deshpande LM, Mendes RE, Canton R, Sader HS, Jones RN. Variations in the occurrence of resistance phenotypes and carbapenemase genes among Enterobacteriaceae isolates in 20 Years of the SENTRY Antimicrobial Surveillance Program. Open Forum Infect Dis 2019; 15(Suppl. 1):S23-S33. https://doi. org/10.1093/ofid/ofy347.
Bou G. Relación entre resistencia y virulencia en bacterias de interés clínico. Enferm Infecc Microbiol Clin 2014; 32(1):1-3. https://doi.org/10.1016/j.eimc.2013.11.002.
Beceiro A, Tomás M, Bou G. Antimicrobial resistance and virulence: a successful or deleterious association in the bacterial world? Clin Microbiol Rev 2013; 26(2):185-230. https://doi.org/10.1128/CMR.00059-12.
Chouduri A, Wadud A, Islam A. Extended spectrum multi-drug resistance versus pathogenic factors- swarming, proteases, and urease-of Proteus species. Int Res J Microbiol 2014; 5(1):8-15. https://doi.org/ 10.14303/irjm.2013.052.
Published
2021-03-22
How to Cite
Rodulfo, H., Horta, M., Mata, G., Gutiérrez, R., González, Y., Michelli, E., Guzman, M., Martínez, D., Sharma, A., & De Donato, M. (2021). Negative correlation between virulence and multidrug resistance in intrahospital and community acquired infections by Proteus mirabilis, in Eastern Venezuela.: Correlación negativa entre la viruluencia y la resistencia multidroga en infecciones intrahospitalarias y adquiridas en la comunidad por Proteus mirabilis, en el Oriente de Venezuela. Investigación Clínica, 62(1), 37-51. https://doi.org/10.22209/IC.v62n1a04
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