Generic placeholder image

Infectious Disorders - Drug Targets

Author(s): Raquel Soares da Silva, Felipe Crepaldi Duarte, Tiago Danelli, Anna Paula Silva Olak, Gerusa Luciana Gomes Magalhães, Marsileni Pelisson, Stefani Lino Cardim, Guilherme Bartolomeu Gonçalves, Eliana Carolina Vespero, Eliandro Reis Tavares, Lucy Megumi Yamauchi, Marcia Regina Eches Perugini and Sueli Fumie Yamada-Ogatta*

DOI: 10.2174/1871526522666220823164600

DownloadDownload PDF Flyer Cite As
High Prevalence of Panton-valentine Leukocidin-encoding Genes in Methicillin-resistant Staphylococcus aureus Isolated from Inpatients with Invasive Infections at a University Hospital in Southern Brazil

Article ID: e230822207951 Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: Staphylococcus aureus is a major cause of a wide diversity of infections in humans, and the expression of Panton-Valentine Leukocidin (PVL) has been associated with severe clinical syndromes.

Objectives: The present study aimed to investigate the prevalence of PVL-encoding genes in S. aureus isolated from clinical samples of inpatients with invasive infections in a teaching hospital in Southern Brazil. Furthermore, phenotypic and genotypic characteristics of bacterial isolates were analyzed.

Methods: A total of 98 S. aureus isolates recovered from different body sites were characterized according to their antimicrobial susceptibility profile, methicillin-resistance and SCCmec typing, genetic relatedness and occurrence of virulence-encoding genes, such as icaA, lukS-PV/lukF-PV, and tst.

Results: Sixty-eight (69.4%) isolates were classified as methicillin-resistant, and among them, four (5.9%) did not harbor the mecA gene. The mecA-harboring methicillin-resistant S. aureus (MRSA) isolates were grouped into SCCmec types I (6.3%), II (64.1%), III (6.3%), IV (15.6%), V (4.7%), and VI (1.6%). One isolate (1.6%) was classified as non-typeable (NT). Seventy isolates (71.4%) were classified as multidrug-resistant. The overall prevalence of virulence-encoding genes was as follows: icaA, 99.0%; tst, 27.5%; and lukS-PV/lukF-PV, 50.0%. The presence of tst gene was significantly higher (p < 0.001) in methicillin-susceptible S. aureus (MSSA) compared to MRSA isolates.

Conclusion: The present study reports a high prevalence of multidrug-resistant S. aureus harboring lukS-PV/lukF-PV and tst genes in invasive infections. The continuous monitoring of the antimicrobial susceptibility profile and virulence of S. aureus is an important measure for the control of infections caused by this bacterium.

Keywords: Multidrug-resistance, SCCmec typing, rep-PCR fingerprinting, toxic shock syndrome toxin, intercellular adhesion locus

Graphical Abstract

[1]
Krismer B, Weidenmaier C, Zipperer A, Peschel A. The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota. Nat Rev Microbiol 2017; 15(11): 675-87.
[http://dx.doi.org/10.1038/nrmicro.2017.104] [PMID: 29021598]
[2]
Lowy FD. Staphylococcus aureus infections. N Engl J Med 1998; 339(8): 520-32.
[http://dx.doi.org/10.1056/NEJM199808203390806] [PMID: 9709046]
[3]
Rammelkamp CH, Maxon T. Resistance of Staphylococcus aureus to the action of penicillin. Exp Biol Med (Maywood) 1942; 51(3): 386-9.
[http://dx.doi.org/10.3181/00379727-51-13986]
[4]
Jevons MP. “Celbenin” - resistant Staphylococci. BMJ 1961; 1(5219): 124-5.
[http://dx.doi.org/10.1136/bmj.1.5219.124-a]
[5]
Lakhundi S, Zhang K. Methicillin-resistant Staphylococcus aureus: Molecular characterization, evolution, and epidemiology. Clin Microbiol Rev 2018; 31(4): e00020-18.
[http://dx.doi.org/10.1128/CMR.00020-18] [PMID: 30209034]
[6]
Turner NA, Sharma-Kuinkel BK, Maskarinec SA, et al. Methicillin-resistant Staphylococcus aureus: An overview of basic and clinical research. Nat Rev Microbiol 2019; 17(4): 203-18.
[http://dx.doi.org/10.1038/s41579-018-0147-4] [PMID: 30737488]
[7]
Andrade MM, Luiz WB, da Silva Oliveira Souza R, Amorim JH. The history of methicillin-resistant Staphylococcus aureus in Brazil. Can J Infect Dis Med Microbiol 2020; 2020: 1-18.
[http://dx.doi.org/10.1155/2020/1721936] [PMID: 33082892]
[8]
Aratani T, Tsukamoto H, Higashi T, et al. Association of methicillin resistance with mortality of hospital-acquired Staphylococcus aureus bacteremia. J Int Med Res 2021; 49(11)
[http://dx.doi.org/10.1177/03000605211058872] [PMID: 34826374]
[9]
Saravolatz LD, Markowitz N, Arking L, Pohlod D, Fisher E. Methicillin-Resistant Staphylococcus aureus. Ann Intern Med 1982; 96(1): 11-6.
[http://dx.doi.org/10.7326/0003-4819-96-1-11] [PMID: 7053683]
[10]
Tenover FC, Goering RV. Methicillin-resistant Staphylococcus aureus strain USA300: Origin and epidemiology. J Antimicrob Chemother 2009; 64(3): 441-6.
[http://dx.doi.org/10.1093/jac/dkp241] [PMID: 19608582]
[11]
Vandenesch F, Naimi T, Enright MC, et al. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: Worldwide emergence. Emerg Infect Dis 2003; 9(8): 978-84.
[http://dx.doi.org/10.3201/eid0908.030089] [PMID: 12967497]
[12]
Calfee DP. Trends in community versus health care-acquired methicillin-resistant Staphylococcus aureus infections. Curr Infect Dis Rep 2017; 19(12): 48.
[http://dx.doi.org/10.1007/s11908-017-0605-6] [PMID: 29101576]
[13]
Saeed K, Gould I, Esposito S, et al. Panton–Valentine leukocidin-positive Staphylococcus aureus: A position statement from the International Society of Chemotherapy. Int J Antimicrob Agents 2018; 51(1): 16-25.
[http://dx.doi.org/10.1016/j.ijantimicag.2017.11.002] [PMID: 29174420]
[14]
Tajik S, Najar-Peerayeh S, Bakhshi B. Hospital clones of Panton-Valentine leukocidin-positive and methicillin-resistant Staphylococcus aureus circulating in the Tehran community. J Glob Antimicrob Resist 2020; 22: 177-81.
[http://dx.doi.org/10.1016/j.jgar.2019.12.010] [PMID: 31874221]
[15]
Sicot N, Khanafer N, Meyssonnier V, et al. Methicillin resistance is not a predictor of severity in community-acquired Staphylococcus aureus necrotizing pneumonia—results of a prospective observational study. Clin Microbiol Infect 2013; 19(3): E142-8.
[http://dx.doi.org/10.1111/1469-0691.12022] [PMID: 23237492]
[16]
Gillet Y, Henry T, Vandenesch F. Fulminant Staphylococcal infections. Microbiol Spectr 2018; 6(5): 6.5.09.
[http://dx.doi.org/10.1128/microbiolspec.GPP3-0036-2018] [PMID: 30291703]
[17]
Yokomori R, Tsurukiri J, Moriya M, et al. First report of fatal infection caused by community-acquired methicillin-resistant Staphylococcus aureus USA300 clone in a collegiate athlete. Japan Med Assoc J 2020; 3(1): 78-82.
[http://dx.doi.org/10.31662/jmaj.2019-0054] [PMID: 33324780]
[18]
Amin DHM, Guler E, Baddal B. Prevalence of panton-valentine leukocidin in methicillin-resistant Staphylococcus aureus clinical isolates at a university hospital in northern cyprus: A pilot study. BMC Res Notes 2020; 13(1): 490.
[http://dx.doi.org/10.1186/s13104-020-05339-0] [PMID: 33081819]
[19]
Iliya S, Mwangi J, Maathai R, Muriuki M, Wainaina C. Molecular detection of Panton-Valentine leukocidin toxin in clinical isolates of Staphylococcus aureus from Kiambu County, Kenya. Int J Microbiol 2020; 2020: 1-8.
[http://dx.doi.org/10.1155/2020/3106747] [PMID: 32908521]
[20]
Klein S, Hannesen J, Zanger P, Heeg K, Boutin S, Nurjadi D. Entry of Panton–Valentine leukocidin-positive methicillin-resistant Staphylo-coccus aureus into the hospital: Prevalence and population structure in Heidelberg, Germany 2015–2018. Sci Rep 2020; 10(1): 13243.
[http://dx.doi.org/10.1038/s41598-020-70112-z] [PMID: 32764618]
[21]
McGuinness SL, Holt DC, Harris TM, et al. Clinical and molecular epidemiology of an emerging Panton-Valentine leukocidin-positive ST5 methicillin-resistant Staphylococcus aureus clone in Northern Australia. MSphere 2021; 6(1): e00651-20.
[http://dx.doi.org/10.1128/mSphere.00651-20] [PMID: 33568451]
[22]
Duarte FC, Danelli T, Ribeiro MAG, et al. Bacteremia caused by Staphylococcus aureus: A fifteen-year analysis of antimicrobial susceptibility in a tertiary hospital in Brazil. J Epidemiol Infect Control 2018; 8(3): 232-8.
[http://dx.doi.org/10.17058/reci.v8i3.11245]
[23]
Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care–associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008; 36(5): 309-32.
[http://dx.doi.org/10.1016/j.ajic.2008.03.002] [PMID: 18538699]
[24]
Jorgensen JH, Carroll KC, Funke G, Pfaller MA, Landry ML, Richter SS, Eds. Manual of Clinical Microbiology. (11th ed.), Washington, DC: ASM Press 2015.
[25]
Hirotaki S, Sasaki T, Kuwahara-Arai K, Hiramatsu K. Rapid and accurate identification of human-associated Staphylococci by use of multiplex PCR. J Clin Microbiol 2011; 49(10): 3627-31.
[http://dx.doi.org/10.1128/JCM.00488-11] [PMID: 21832022]
[26]
Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing. (29th ed.), Wayne, PA: Clinical and Laboratory Standard Institute 2019.
[27]
EUCAST. The European Committee on Antimicrobial Susceptibility Testing Breakpoint tables for interpretation of MICs and zone diameters. 2019. Available from: http:/www.eucast.org
[28]
Ausubel FM, Brent R, Kingston RE, Eds. Short Protocols in Molecular Biology. 4th ed. Wiley-Blackwell 1999.
[29]
Campbell SJ, Deshmukh HS, Nelson CL, et al. Genotypic characteristics of Staphylococcus aureus isolates from a multinational trial of complicated skin and skin structure infections. J Clin Microbiol 2008; 46(2): 678-84.
[http://dx.doi.org/10.1128/JCM.01822-07] [PMID: 18077636]
[30]
Milheiriço C, Oliveira DC, de Lencastre H. Update to the multiplex PCR strategy for assignment of mec element types in Staphylococcus aureus. Antimicrob Agents Chemother 2007; 51(9): 3374-7.
[http://dx.doi.org/10.1128/AAC.00275-07] [PMID: 17576837]
[31]
Del Vecchio VG, Petroziello JM, Gress MJ, et al. Molecular genotyping of methicillin-resistant Staphylococcus aureus via fluorophore-enhanced repetitive-sequence PCR. J Clin Microbiol 1995; 33(8): 2141-4.
[http://dx.doi.org/10.1128/jcm.33.8.2141-2144.1995] [PMID: 7559964]
[32]
van der Zee A, Verbakel H, van Zon JC, et al. Molecular genotyping of Staphylococcus aureus strains: Comparison of repetitive element sequence-based PCR with various typing methods and isolation of a novel epidemicity marker. J Clin Microbiol 1999; 37(2): 342-9.
[http://dx.doi.org/10.1128/JCM.37.2.342-349.1999] [PMID: 9889215]
[33]
Heras J, Domínguez C, Mata E, et al. GelJ – a tool for analyzing DNA fingerprint gel images. BMC Bioinformatics 2015; 16(1): 270.
[http://dx.doi.org/10.1186/s12859-015-0703-0] [PMID: 26307353]
[34]
Oliveira CF, Morey AT, Santos JP, et al. Molecular and phenotypic characteristics of methicillin-resistant Staphylococcus aureus isolated from hospitalized patients. J Infect Dev Ctries 2015; 9(7): 743-51.
[http://dx.doi.org/10.3855/jidc.5868] [PMID: 26230125]
[35]
Lisowska-Łysiak K, Lauterbach R, Międzobrodzki J, Kosecka-Strojek M. Epidemiology and pathogenesis of Staphylococcus bloodstream infections in humans: A review. Pol J Microbiol 2021; 70(1): 13-23.
[http://dx.doi.org/10.33073/pjm-2021-005] [PMID: 33815523]
[36]
Kuehl R, Morata L, Boeing C, et al. Defining persistent Staphylococcus aureus bacteraemia: Secondary analysis of a prospective cohort study. Lancet Infect Dis 2020; 20(12): 1409-17.
[http://dx.doi.org/10.1016/S1473-3099(20)30447-3] [PMID: 32763194]
[37]
Wächter H, Yörük E, Becker K, Görlich D, Kahl BC. Correlations of host and bacterial characteristics with clinical parameters and survival in Staphylococcus aureus bacteremia. J Clin Med 2021; 10(7): 1371.
[http://dx.doi.org/10.3390/jcm10071371] [PMID: 33800644]
[38]
Cheung GYC, Bae JS, Otto M. Pathogenicity and virulence of Staphylococcus aureus. Virulence 2021; 12(1): 547-69.
[http://dx.doi.org/10.1080/21505594.2021.1878688] [PMID: 33522395]
[39]
Guo Y, Song G, Sun M, Wang J, Wang Y. Prevalence and therapies of antibiotic-resistance in Staphylococcus aureus. Front Cell Infect Microbiol 2020; 10: 107.
[http://dx.doi.org/10.3389/fcimb.2020.00107] [PMID: 32257966]
[40]
Miklasińska-Majdanik M. Mechanisms of resistance to macrolide antibiotics among Staphylococcus aureus. Antibiotics (Basel) 2021; 10(11): 1406.
[http://dx.doi.org/10.3390/antibiotics10111406]
[41]
Leclercq R, Courvalin P. Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification. Antimicrob Agents Chemother 1991; 35(7): 1267-72.
[http://dx.doi.org/10.1128/AAC.35.7.1267] [PMID: 1929280]
[42]
Magiorakos AP, Srinivasan A, Carey RB, et al. 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): 268-81.
[http://dx.doi.org/10.1111/j.1469-0691.2011.03570.x] [PMID: 21793988]
[43]
Bodnar GC, Martins HM, De Oliveira CF, et al. Comparison of HRM analysis and three REP-PCR genomic fingerprint methods for rapid typing of MRSA at a Brazilian hospital. J Infect Dev Ctries 2016; 10(12): 1306-17.
[http://dx.doi.org/10.3855/jidc.7887] [PMID: 28036310]
[44]
Duarte FC, Tavares ER, Danelli T, et al. Disseminated Clonal Complex 5 (CC5) methicillin-resistant Staphylococcus aureus SCCmec type II in a tertiary hospital of Southern Brazil. Rev Inst Med Trop São Paulo 2018; 60(0): e32.
[http://dx.doi.org/10.1590/s1678-9946201860032] [PMID: 30043936]
[45]
Okado JB, Avaca-Crusca JS, Oliveira AL, Dabul ANG, Camargo ILBC. Daptomycin and vancomycin heteroresistance revealed among CC5-SCCmecII MRSA clone and in vitro evaluation of treatment alternatives. J Glob Antimicrob Resist 2018; 14: 209-16.
[http://dx.doi.org/10.1016/j.jgar.2018.05.001] [PMID: 29753135]
[46]
Bride LL, Pereira MF, Barbosa MC, et al. Differences in resistance profiles and virulence genes among methicillin-resistant and methicillin-susceptible Staphylococcus aureus of different lineages at a public tertiary hospital. Rev Soc Bras Med Trop 2019; 52: e20190095.
[http://dx.doi.org/10.1590/0037-8682-0095-2019] [PMID: 31340369]
[47]
Nascimento TC, Diniz CG, Silva VL, et al. Methicillin-resistant Staphylococcus aureus isolated from an intensive care unit in Minas Gerais, Brazil, over a six-year period. Braz J Infect Dis 2018; 22(1): 55-9.
[http://dx.doi.org/10.1016/j.bjid.2017.10.004] [PMID: 29169012]
[48]
Machado TS, Pinheiro FR, Andre LSP, et al. Virulence factors found in nasal colonization and infection of methicillin-resistant Staphylococcus aureus (MRSA) isolates and their ability to form a biofilm. Toxins (Basel) 2020; 13(1): 14.
[http://dx.doi.org/10.3390/toxins13010014] [PMID: 33375552]
[49]
Arias CA, Reyes J, Carvajal LP, et al. A prospective cohort multicenter study of molecular epidemiology and phylogenomics of staphylococcus aureus bacteremia in nine latin American countries. Antimicrob Agents Chemother 2017; 61(10): e00816-7.
[http://dx.doi.org/10.1128/AAC.00816-17]
[50]
Jariyasethpong T, Tribuddharat C, Dejsirilert S, et al. MRSA carriage in a tertiary governmental hospital in Thailand: Emphasis on prevalence and molecular epidemiology. Eur J Clin Microbiol Infect Dis 2010; 29(8): 977-85.
[http://dx.doi.org/10.1007/s10096-010-0954-7] [PMID: 20509037]
[51]
Maeda R, Kobayashi H, Higashidani M, et al. Molecular epidemiological and pharmaceutical studies of methicillin-resistant Staphylococcus aureus isolated at hospitals in Kure City, Japan. Access Microbiol 2022; 4(2): 000319.
[http://dx.doi.org/10.1099/acmi.0.000319] [PMID: 35355871]
[52]
Silva V, Hermenegildo S, Ferreira C, et al. Genetic characterization of methicillin-resistant Staphylococcus aureus isolates from human bloodstream infections: Detection of MLSB resistance. Antibiotics (Basel) 2020; 9(7): 375.
[http://dx.doi.org/10.3390/antibiotics9070375] [PMID: 32635147]
[53]
Cramton SE, Gerke C, Schnell NF, Nichols WW, Götz F. The intercellular adhesion (ICA) locus is present in Staphylococcus aureus and is required for biofilm formation. Infect Immun 1999; 67(10): 5427-33.
[http://dx.doi.org/10.1128/IAI.67.10.5427-5433.1999] [PMID: 10496925]
[54]
Rohde H, Frankenberger S, Zähringer U, Mack D. Structure, function and contribution of polysaccharide intercellular adhesin (PIA) to Staphylococcus epidermidis biofilm formation and pathogenesis of biomaterial-associated infections. Eur J Cell Biol 2010; 89(1): 103-11.
[http://dx.doi.org/10.1016/j.ejcb.2009.10.005] [PMID: 19913940]
[55]
Otto M. Staphylococcal biofilms. Microbiol Spectr 2018; 6(4)
[http://dx.doi.org/10.1128/microbiolspec.GPP3-0023-2018]
[56]
Yousif A, Jamal MA, Raad I. Biofilm-based central line-associated bloodstream infections. Adv Exp Med Biol 2015; 830: 157-79.
[http://dx.doi.org/10.1007/978-3-319-11038-7_10] [PMID: 25366227]
[57]
Kaneko J, Kamio Y. Bacterial two-component and hetero-heptameric pore-forming cytolytic toxins: Structures, pore-forming mechanism, and organization of the genes. Biosci Biotechnol Biochem 2004; 68(5): 981-1003.
[http://dx.doi.org/10.1271/bbb.68.981] [PMID: 15170101]
[58]
König B, Prévost G, Piémont Y, König W. Effects of Staphylococcus aureus leukocidins on inflammatory mediator release from human granulocytes. J Infect Dis 1995; 171(3): 607-13.
[http://dx.doi.org/10.1093/infdis/171.3.607] [PMID: 7533198]
[59]
Spaan AN, van Strijp JAG, Torres VJ. Leukocidins: Staphylococcal bi-component pore-forming toxins find their receptors. Nat Rev Microbiol 2017; 15(7): 435-47.
[http://dx.doi.org/10.1038/nrmicro.2017.27] [PMID: 28420883]
[60]
Wang R, Braughton KR, Kretschmer D, et al. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med 2007; 13(12): 1510-4.
[http://dx.doi.org/10.1038/nm1656] [PMID: 17994102]
[61]
Novick RP, Ram G. Staphylococcal pathogenicity islands — movers and shakers in the genomic firmament. Curr Opin Microbiol 2017; 38: 197-204.
[http://dx.doi.org/10.1016/j.mib.2017.08.001] [PMID: 29100762]
[62]
Xu SX, McCormick JK. Staphylococcal superantigens in colonization and disease. Front Cell Infect Microbiol 2012; 2: 52.
[http://dx.doi.org/10.3389/fcimb.2012.00052] [PMID: 22919643]
[63]
Peng L, Jiang J, Chen T, et al. Toxic shock syndrome toxin 1 induces immune response via the activation of NLRP3 inflammasome. Toxins (Basel) 2021; 13(1): 68.
[http://dx.doi.org/10.3390/toxins13010068] [PMID: 33477467]
[64]
Schlievert PM, Davis CC. Device-associated menstrual toxic shock syndrome. Clin Microbiol Rev 2020; 33(3): e00032-19.
[http://dx.doi.org/10.1128/CMR.00032-19] [PMID: 32461307]
[65]
Kim D, Hong JS, Yoon EJ, et al. Toxic shock syndrome toxin 1-producing methicillin-resistant Staphylococcus aureus of clonal complex 5, the new york/japan epidemic clone, causing a high early-mortality rate in patients with bloodstream infections. Antimicrob Agents Chemother 2019; 63(11): e01362-19.
[http://dx.doi.org/10.1128/AAC.01362-19] [PMID: 31501145]
[66]
Otter JA, French GL. Community-associated meticillin-resistant Staphylococcus aureus: The case for a genotypic definition. J Hosp Infect 2012; 81(3): 143-8.
[http://dx.doi.org/10.1016/j.jhin.2012.04.009] [PMID: 22622448]