Skip to main content

Advertisement

Log in

Genotyping of methicillin-resistant Staphylococcus aureus from sepsis patients in Pakistan and detection of antibodies against staphylococcal virulence factors

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

In order to obtain more information on the MRSA population structure in the border region of Afghanistan and Pakistan, we collected and genotyped MRSA causing bloodstream infections from a tertiary care hospital in Peshawar, Pakistan, that serves the local population as well as Afghan immigrants and refugees. Thirty-one MRSA isolates from 30 patients were included and characterized by microarray hybridisation. For 25 patients, serum samples were tested using protein microarrays in order to detect antibodies against staphylococcal virulence factors. The most conspicuous result was the high rate of PVL-positive MRSA. Twenty-two isolates (71%) harboured lukF/S-PV genes. The most common lineage was CC772-MRSA-V/VT (PVL+) to which eleven isolates were assigned. The second most common strain was, surprisingly, CC8-MRSA-[IV+ACME] (PVL+), “USA300” (9 isolates). Two isolates were tst1 positive CC22-MRSA-IV, matching the Middle Eastern “Gaza Epidemic Strain”. Another two were PVL-positive CC30-MRSA-IV. The remaining isolates belonged to, possibly locally emerging, CC1, CC5, and CC8 strains with SCC mec IV elements. Twenty-three patient sera were positive for anti-PVL-IgG antibodies. Several questions arise from the present study. It can be assumed that MRSA and high rates of PVL-positive S. aureus/MRSA are a public health issue in the Afghanistan/Pakistan border region. A possible emergence of the “USA300” clone as well as of the CC772 lineage warrants further investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Naimi HM, Rasekh H, Noori AZ, Bahaduri MA (2017) Determination of antimicrobial susceptibility patterns in Staphylococcus aureus strains recovered from patients at two main health facilities in Kabul, Afghanistan. BMC Infect Dis 17(1):737

    Article  Google Scholar 

  2. Tariq TM (2014) Bacteriologic profile and antibiogram of blood culture isolates from a children's hospital in Kabul. J Coll Physicians Surg Pak 24(6):396–399

    PubMed  Google Scholar 

  3. Aro T, Kantele A (2018) High rates of meticillin-resistant Staphylococcus aureus among asylum seekers and refugees admitted to Helsinki University hospital, 2010 to 2017. Euro Surveill 23(45)

  4. Murray CK, Yun HC, Griffith ME, Thompson B, Crouch HK, Monson LS, Aldous WK, Mende K, Hospenthal DR (2009) Recovery of multidrug-resistant bacteria from combat personnel evacuated from Iraq and Afghanistan at a single military treatment facility. Mil Med 174(6):598–604

    Article  Google Scholar 

  5. Vento TJ, Calvano TP, Cole DW, Mende K, Rini EA, Tully CC, Landrum ML, Zera W, Guymon CH, Yu X, Beckius ML, Cheatle KA, Murray CK (2013) Staphylococcus aureus colonization of healthy military service members in the United States and Afghanistan. BMC Infect Dis 13:325

    Article  Google Scholar 

  6. Arfat Y (2013) Genotyping of methicillin resistant Staphylococcus aureus (MRSA) from local hospital of Rawalpindi/Islamabad, Pakistan. Local Hospital of Rawalpindi/Islamabad. Quaid-i-Azam University, Islamabad, Islamabad

    Google Scholar 

  7. Jamil B, Gawlik D, Syed MA, Shah AA, Abbasi SA, Müller E, Reißig A, Ehricht R, Monecke S (2017) Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) from Pakistan: molecular characterisation by microarray technology. Eur J Clin Microbiol Infect Dis

  8. Khan S, Sung K, Iram S, Nawaz M, Xu J, Marasa B (2016) Draft genome sequences of two methicillin-resistant clinical Staphylococcus aureus isolates. Genome Announc 4(1)

  9. Madzgalla S, Syed MA, Khan MA, Rehman SS, Muller E, Reissig A, Ehricht R, Monecke S (2016) Molecular characterization of Staphylococcus aureus isolates causing skin and soft tissue infections in patients from Malakand, Pakistan. Eur J Clin Microbiol Infect Dis 35(9):1541–1547

    Article  CAS  Google Scholar 

  10. Monecke S, Slickers P, Gawlik D, Müller E, Reissig A, Ruppelt-Lorz A, Akpaka P, Bandt D, Bes M, Boswihi S, Coleman D, Coombs G, Dorneanu O, Gostev V, Ip M, Jamil B, Jatzwauk L, Narvaez M, Roberts R, Senok A, Shore A, Sidorenko S, Skakni L, Somily A, Syed M, Thürmer A, Udo E, Vremeră T, Zurita J, Ehricht R (2018) Molecular typing of ST239-MRSA-III from diverse geographic locations and the evolution of the SCCmec III element during its intercontinental spread. Front Microbiol 9(1436)

  11. Naeem I, Naqvi BS, Hashmi K, Gauhar S (2006) Paediatric nosocomial infections: resistance pattern of clinical isolates. Pak J Pharm Sci 19(1):52–57

    PubMed  Google Scholar 

  12. Shabir S, Hardy KJ, Abbasi WS, McMurray CL, Malik SA, Wattal C, Hawkey PM (2010) Epidemiological typing of meticillin-resistant Staphylococcus aureus isolates from Pakistan and India. J Med Microbiol 59(Pt 3):330–337

    Article  CAS  Google Scholar 

  13. Zafar A, Stone M, Ibrahim S, Parveen Z, Hasan Z, Khan E, Hasan R, Wain J, Bamford K (2011) Prevalent genotypes of meticillin-resistant Staphylococcus aureus: report from Pakistan. J Med Microbiol 60(Pt 1):56–62

    Article  CAS  Google Scholar 

  14. Wiese L, Mejer N, Schønheyder HC, Westh H, Jensen AG, Larsen AR, Skov R, Benfield T (2013) A nationwide study of comorbidity and risk of reinfection after Staphylococcus aureus bacteraemia. J Infect 67(3):199–205

    Article  CAS  Google Scholar 

  15. Kupfer M, Jatzwauk L, Monecke S, Mobius J, Weusten A (2010) MRSA in a large German University hospital: male gender is a significant risk factor for MRSA acquisition. GMS Krankenhhyg Interdiszip 5(2)

  16. Monecke S, Coombs G, Shore AC, Coleman DC, Akpaka P, Borg M, Chow H, Ip M, Jatzwauk L, Jonas D, Kadlec K, Kearns A, Laurent F, O'Brien FG, Pearson J, Ruppelt A, Schwarz S, Scicluna E, Slickers P, Tan H-L, Weber S, Ehricht R (2011) A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant Staphylococcus aureus. PLoS One 6(4):e17936

    Article  CAS  Google Scholar 

  17. Monecke S, Slickers P, Ehricht R (2008) Assignment of Staphylococcus aureus isolates to clonal complexes based on microarray analysis and pattern recognition. FEMS Immunol Med Microbiol 53:237–251

    Article  CAS  Google Scholar 

  18. Monecke S, Jatzwauk L, Müller E, Nitschke H, Pfohl K, Slickers P, Reissig A, Ruppelt-Lorz A, Ehricht R (2016) Diversity of SCCmec elements in Staphylococcus aureus as observed in south-eastern Germany. PLoS One 11(9):e0162654

    Article  Google Scholar 

  19. Selle M, Hertlein T, Oesterreich B, Klemm T, Kloppot P, Müller E, Ehricht R, Stentzel S, Broker BM, Engelmann S, Ohlsen K (2016) Global antibody response to Staphylococcus aureus live-cell vaccination. Sci Rep 6:24754

    Article  CAS  Google Scholar 

  20. Stieber B, Monecke S, Müller E, Büchler J, Ehricht R (2015) Direct, specific and rapid detection of staphylococcal proteins and exotoxins using a multiplex antibody microarray. PLoS One 10(12):e0143246

    Article  Google Scholar 

  21. Kohler C, Dunachie SJ, Müller E, Kohler A, Jenjaroen K, Teparrukkul P, Baier V, Ehricht R, Steinmetz I (2016) Rapid and sensitive multiplex detection of Burkholderia pseudomallei-specific antibodies in melioidosis patients based on a protein microarray approach. PLoS Negl Trop Dis 10(7):e0004847

    Article  Google Scholar 

  22. Novick RP (2003) Mobile genetic elements and bacterial toxinoses: the superantigen-encoding pathogenicity islands of Staphylococcus aureus. Plasmid 49(2):93–105

    Article  CAS  Google Scholar 

  23. Vojtov N, Ross HF, Novick RP (2002) Global repression of exotoxin synthesis by staphylococcal superantigens. Proc Natl Acad Sci U S A 99(15):10102–10107

    Article  CAS  Google Scholar 

  24. Stieber B, Monecke S, Müller E, Baier V, Coombs G, Ehricht R (2013) Development and usage of protein microarrays for the quantitative measurement of Panton-Valentine leukocidin. Mol Cell Probes

  25. McCaskill ML, Mason EO Jr, Kaplan SL, Hammerman W, Lamberth LB, Hulten KG (2007) Increase of the USA300 clone among community-acquired methicillin-susceptible Staphylococcus aureus causing invasive infections. Pediatr Infect Dis J 26(12):1122–1127

    Article  Google Scholar 

  26. Miko BA, Uhlemann AC, Gelman A, Lee CJ, Hafer CA, Sullivan SB, Shi Q, Miller M, Zenilman J, Lowy FD (2012) High prevalence of colonization with Staphylococcus aureus clone USA300 at multiple body sites among sexually transmitted disease clinic patients: an unrecognized reservoir. Microbes Infect 14(12):1040–1043

    Article  Google Scholar 

  27. Seybold U, Kourbatova EV, Johnson JG, Halvosa SJ, Wang YF, King MD, Ray SM, Blumberg HM (2006) Emergence of community-associated methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of health care-associated blood stream infections. Clin Infect Dis 42(5):647–656

    Article  CAS  Google Scholar 

  28. Weber S, Ehricht R, Slickers P, Abdel-Wareth L, Donnelly G, Pitout M, Monecke S (2010) Genetic fingerprinting of MRSA from Abu Dhabi. ECCMID, Vienna

    Google Scholar 

  29. Senok A, Ehricht R, Monecke S, Al-Saedan R, Somily A (2016) Molecular characterization of methicillin-resistant Staphylococcus aureus in nosocomial infections in a tertiary-care facility: emergence of new clonal complexes in Saudi Arabia. New Microbes New Infect 14:13–18

    Article  CAS  Google Scholar 

  30. Uhlemann AC, Kennedy AD, Martens C, Porcella SF, Deleo FR, Lowy FD (2012) Toward an understanding of the evolution of Staphylococcus aureus strain USA300 during colonization in community households. Genome Biol Evol 4(12):1275–1285

    Article  Google Scholar 

  31. Monecke S, Ehricht R, Slickers P, Tan HL, Coombs G (2009) The molecular epidemiology and evolution of the Panton-Valentine leukocidin-positive, methicillin-resistant Staphylococcus aureus strain USA300 in Western Australia. Clin Microbiol Infect 15(8):770–776

    Article  CAS  Google Scholar 

  32. Earls MR, Shore AC, Brennan GI, Simbeck A, Schneider-Brachert W, Vremerǎ T, Dorneanu OS, Slickers P, Ehricht R, Monecke S, Coleman DC (2019) A novel multidrug-resistant PVL-negative CC1-MRSA-IV clone emerging in Ireland and Germany likely originated in South-Eastern Europe. Infect Genet Evol 69:117–126

    Article  CAS  Google Scholar 

  33. Senok A, Somily A, Raji A, Gawlik D, Al-Shahrani F, Baqi S, Boswihi S, Skakni L, Udo EE, Weber S, Ehricht R, Monecke S (2016) Diversity of methicillin-resistant Staphylococcus aureus CC22-MRSA-IV from Saudi Arabia and the Gulf region. Int J Infect Dis 51:31–35

    Article  CAS  Google Scholar 

  34. Monecke S, Müller E, Buechler J, Rejman J, Stieber B, Akpaka PE, Bandt D, Burris R, Coombs G, Hidalgo-Arroyo GA, Hughes P, Kearns A, Abos SM, Pichon B, Skakni L, Soderquist B, Ehricht R (2013) Rapid detection of Panton-Valentine leukocidin in Staphylococcus aureus cultures by use of a lateral flow assay based on monoclonal antibodies. J Clin Microbiol 51(2):487–495

    Article  CAS  Google Scholar 

  35. Rasigade JP, Trouillet-Assant S, Breurec S, Antri K, Lina G, Bes M, Tristan A, Badiou C, Bernelin M, Fall C, Ramdani-Bouguessa N, Etienne J, Vandenesch F, Laurent F (2015) The levels of antibodies to Panton-Valentine leukocidin (PVL) vary with PVL prevalence along a north-to-south gradient. Eur J Clin Microbiol Infect Dis 34(5):927–933

    Article  CAS  Google Scholar 

  36. Ji-Young P, Jae-Seok K, Heungjeong W (2015) Prevalence of antibody to toxic shock syndrome toxin-1 in burn patients. Ann Lab Med 35(1):89–93

    Article  Google Scholar 

  37. Quan L, Morita R, Kawakami S (2010) Toxic shock syndrome toxin-1 (TSST-1) antibody levels in Japanese children. Burns 36(5):716–721

    Article  Google Scholar 

  38. Parsonnet J, Goering RV, Hansmann MA, Jones MB, Ohtagaki K, Davis CC, Totsuka K (2008) Prevalence of toxic shock syndrome toxin 1 (TSST-1)-producing strains of Staphylococcus aureus and antibody to TSST-1 among healthy Japanese women. J Clin Microbiol 46(8):2731–2738

    Article  Google Scholar 

  39. Albrecht N, Jatzwauk L, Slickers P, Ehricht R, Monecke S (2011) Clonal replacement of epidemic methicillin-resistant Staphylococcus aureus strains in a German university hospital over a period of eleven years. PLoS One 6(11):e28189

    Article  CAS  Google Scholar 

  40. D'Souza N, Rodrigues C, Mehta A (2010) Molecular characterization of methicillin resistant Staphylococcus aureus (MRSA) with emergence of epidemic clones ST 22 and ST 772, in Mumbai, India. J Clin Microbiol 48(5):1806–1811

    Article  Google Scholar 

Download references

Acknowledgments

The authors thank Peter Slickers (Abbott/Alere Jena) for bioinformatic work designing the microarrays used for the present study. We would like to acknowledge the staff of Lady Reading Hospital Peshawar for their cooperation in sample collection.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stefan Monecke.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Supplemental file 1

Full genotyping data. (PDF 1065 kb)

Supplemental file 2A

Full serological data (direct assay). (PDF 267 kb)

Supplemental file 2B

Full serological data (indirect assay). (PDF 263 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Monecke, S., Syed, M.A., Khan, M.A. et al. Genotyping of methicillin-resistant Staphylococcus aureus from sepsis patients in Pakistan and detection of antibodies against staphylococcal virulence factors. Eur J Clin Microbiol Infect Dis 39, 85–92 (2020). https://doi.org/10.1007/s10096-019-03695-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-019-03695-9

Keywords

Navigation