Characterization of resistance genes to macrolides, lincosamides and streptogramins (MLS) among clinical isolates of Staphylococcus aureus in North Lebanon


  • Marwan Osman Centre AZM pour la recherche en biotechnologies et ses applications, Université Libanaise, Laboratoire de Microbiologie Santé et Environnement (LMSE), Tripoli, Lebanon. Faculty of Public Health, Université Libanaise, Lebanon
  • Azza Al Nasbeh
  • Rayane Rafei
  • Hassan Mallat
  • Marcel Achkar
  • Fouad Dabboussi
  • Monzer Hamze



Staphylococcus aureus, Macrolides, antimicrobial resistance, ermC, msrA, Lebanon


Background. – Staphylococcus aureus is one of the most significant pathogens causing significant morbidity and mortality. Moreover, the incidence of MLS-resistant Staphylococcus aureus infections continues to grow globally.

Objective. – The aim of this study is to examine the expression of resistance of Staphylococcus aureus (S. aureus) isolates to MLS and the prevalence of genes involved in this resistance by PCR.
Methods. – 38 strains of S. aureus MLS-resistant (resistant at least for one macrolide) were isolated in the sector of microbiology at Nini Hospital in North Lebanon. The disk diffusion method was used to determine the phenotype of the MLS resistance. The resistance genes involved were detected by PCR using specific gene primers for ermA, ermB, ermC, msrA, linA, mefA, vat and vgb genes.

Results. – A total of 55.3% of the isolates were positive for inducible phenotype (iMLSB), 15.8% for the constitutive phenotype (cMLSB), 23.7% for MSB phenotype and 5.2% for L phenotype. The ermC gene was the most prevalent (52.6%), while ermA, ermB, msrA and linA genes were observed with lower prevalence. However, a combination of several of these genes was detected. The vgb, vat and mefA genes were not detected in any of the clinical isolates.

Conclusion. – To our knowledge, this study is the first investigation regarding characterization of MLS resistance genes in clinical isolates of S. aureus in Lebanon. The study revealed a high prevalence of the inducible resistance to lincosamides (iMLSB phenotype) and the most prevalent resistance determinants was ermC.

Author Biography

Marwan Osman, Centre AZM pour la recherche en biotechnologies et ses applications, Université Libanaise, Laboratoire de Microbiologie Santé et Environnement (LMSE), Tripoli, Lebanon. Faculty of Public Health, Université Libanaise, Lebanon

Corresponding author


Roberts MC, Sutcliffe J, Courvalin P, Jensen LB, Rood J, Seppala H. Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants. Antimicrob Agents Chemother. 1999; 43: 2823-2830.

Sanchez ML, Flint KK, Jones RN. Occurrence of macrolide-lincosamide-streptogramin resistances among staphylococcal clinical isolates at a university medical center. Is false susceptibility to new macrolides and clindamycin a contemporary clinical and in vitro testing problem? Diagn Microbiol Infect Dis. 1993; 16: 205-213.

Leclercq R. Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications. Clin Infect Dis. 2002; 34: 482-492.

Weisblum B. Erythromycin resistance by ribosome modification. Antimicrob Agents Chemother. 1995; 39: 577-585.

Swenson JM, Brasso WB, Ferraro MJ, Hardy DJ, Knapp CC, McDougal LK, et al. Detection of inducible clindamycin resistance in staphylococci by broth microdilution using erythromycin-clindamycin combination wells. J Clin Microbiol. 2007; 45: 3954-3957.

Clancy J, Petitpas J, Dib-Hajj F, Yuan W, Cronan M, Kamath AV, et al. Molecular cloning and functional analysis of a novel macrolide-resistance determinant, mefA, from Streptococcus pyogenes. Mol Microbiol. 1996; 22: 867-879.

Murphy E. Nucleotide sequence of ermA, a macrolide-lincosamide-streptogramin B determinant in Staphylococcus aureus. J Bacteriol. 1985; 162: 633-640.

Tillotson LE, Jenssen WD, Moon-McDermott L, Dubin DT. Characterization of a novel insertion of the macrolides-lincosamides-streptogramin B resistance transposon Tn554 in methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob Agents Chemother. 1989; 33: 541-550.

Khan SA, Novick RP. Terminal nucleotide sequences of Tn551, a transposon specifying erythromycin resistance in Staphylococcus aureus: homology with Tn3. Plasmid. 1980; 4: 148-154.

Westh H, Hougaard DM, Vuust J, Rosdahl VT. erm genes in erythromycin-resistant Staphylococcus aureus and coagulase-negative staphylococci. APMIS. 1995; 103: 225-232.

Bozdogan B, Berrezouga L, Kuo MS, Yurek DA, Farley KA, Stockman BJ, et al. A new resistance gene, linB, conferring resistance to lincosamides by nucleotidylation in Enterococcus faecium HM1025. Antimicrob Agents Chemother. 1999; 43: 925-929.

Leclercq R, Brisson-Noel A, Duval J, Courvalin P. Phenotypic expression and genetic heterogeneity of lincosamide inactivation in Staphylococcus spp. Antimicrob Agents Chemother. 1987; 31: 1887-1891.

Allignet J, Aubert S, Morvan A, el Solh N. Distribution of genes encoding resistance to streptogramin A and related compounds among staphylococci resistant to these antibiotics. Antimicrob Agents Chemother. 1996; 40: 2523-2528.

Allignet J, Loncle V, Mazodier P, el Solh N. Nucleotide sequence of a staphylococcal plasmid gene, vgb, encoding a hydrolase inactivating the B components of virginiamycin-like antibiotics. Plasmid. 1988; 20: 271-275.

McClure JA, Conly JM, Lau V, Elsayed S, Louie T, Hutchins W, et al. Novel multiplex PCR assay for detection of the staphylococcal virulence marker Panton-Valentine leukocidin genes and simultaneous discrimination of methicillin-susceptible from -resistant staphylococci. J Clin Microbiol. 2006; 44: 1141-1144.

Strommenger B, Kettlitz C, Werner G, Witte W. Multiplex PCR assay for simultaneous detection of nine clinically relevant antibiotic resistance genes in Staphylococcus aureus. J Clin Microbiol. 2003; 41: 4089-4094.

Lina G, Quaglia A, Reverdy ME, Leclercq R, Vandenesch F, Etienne J. Distribution of genes encoding resistance to macrolides, lincosamides, and streptogramins among staphylococci. Antimicrob Agents Chemother. 1999; 43: 1062-1066.

Sutcliffe J, Grebe T, Tait-Kamradt A, Wondrack L. Detection of erythromycin-resistant determinants by PCR. Antimicrob Agents Chemother. 1996; 40: 2562-2566.

Tokajan S. New epidemiology of Staphylococcus aureus infections in the Middle East. Clin Microbiol Infect. 2014; 20: 624-628.

Shehabi AA, Abu-Yousef R, Badran E, Al-Bakri AG, AbuQatouseh LF, Becker K. Major Characteristics of Staphylococcus aureus colonizing Jordanian infants. Pediatr Int. 2013; 55: 300-304.

Khalil W, Hashwa F, Shehabi A, Tokajian S. Methicillin-resistant Staphylococcus aureus ST80-IV clone in children from Jordan. Diagn Microbiol Infect Dis. 2012; 73: 228–230.

El Ayoubi MD, Hamze M, Mallat H, Achkar M, Dabboussi F. Glycopeptide intermediate Staphylococcus aureus and prevalence of the luk-PV gene in clinical isolates, in Northern Lebanon. Med Mal Infect. 2014; 44: 223-228.

Kanj SS, Ghaleb PA, Araj GF. Glycopeptide and oxacillin activity against Staphylococcus aureus isolates at a tertiary care center in Lebanon. J Med Liban. 2004; 52: 8–12.

Chambers HF, Deleo FR. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol. 2009; 7: 629-641.

Prabhu K, Rao S, Rao V. Inducible Clindamycin Resistance in Staphylococcus aureus Isolated from Clinical Samples. J Lab Physicians. 2011; 3: 25-27.

Deotale V, Mendiratta DK, Raut U, Narang P. Inducible clindamycin resistance in Staphylococcus aureus isolated from clinical samples. Indian J Med Microbiol. 2010; 28: 124-126.

Adaleti R, Nakipoglu Y, Ceran N, Tasdemir C, Kaya F, Tasdemir S. Prevalence of phenotypic resistance of Staphylococcus aureus isolates to macrolide, lincosamide, streptogramin B, ketolid and linezolid antibiotics in Turkey. Braz J Infect Dis. 2010; 14: 11-14.

Hamilton-Miller JM, Shah S. Patterns of phenotypic resistance to the macrolide-lincosamide-ketolide-streptogramin group of antibiotics in staphylococci. J Antimicrob Chemother. 2000; 46: 941-949.

Schmitz FJ, Verhoef J, Fluit AC. Prevalence of resistance to MLS antibiotics in 20 European university hospitals participating in the European SENTRY surveillance programme. Sentry Participants Group. J Antimicrob Chemother. 1999; 43: 783-792.

Otsuka T, Zaraket H, Takano T, Saito K, Dohmae S, Higuchi W, et al. Macrolide-lincosamide-streptogramin B resistance phenotypes and genotypes among Staphylococcus aureus clinical isolates in Japan. Clin Microbiol Infect. 2007; 13: 325-327.

Reyes J, Hidalgo M, Diaz L, Rincon S, Moreno J, Vanegas N, et al. Characterization of macrolide resistance in Gram-positive cocci from Colombian hospitals: a countrywide surveillance. Int J Infect Dis. 2007; 11: 329-336.

Fluit AC, Visser MR, Schmitz FJ. Molecular detection of antimicrobial resistance. Clin Microbiol Rev. 2001; 14: 836-871, table of contents.

Sekiguchi J, Fujino T, Saruta K, Konosaki H, Nishimura H, Kawana A, et al. Prevalence of erythromycin-, tetracycline-, and aminoglycoside- resistance genes in methicillin-resistant Staphylococcus aureus in hospitals in Tokyo and Kumamoto. Jpn J Infect Dis. 2004; 57: 74-77.

Martineau F, Picard FJ, Lansac N, Menard C, Roy PH, Ouellette M, et al. Correlation between the resistance genotype determined by multiplex PCR assays and the antibiotic susceptibility patterns of Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob Agents Chemother. 2000; 44: 231-238.

Zmantar T, Chaieb K, Ben Abdallah F, Ben Kahla-Nakbi A, Ben Hassen A, Mahdouani K, et al. Multiplex PCR detection of the antibiotic resistance genes in Staphylococcus aureus strains isolated from auricular infections. Folia Microbiol (Praha). 2008; 53: 357-362.

Spiliopoulou I, Petinaki E, Papandreou P, Dimitracopoulos G. erm(C) is the predominant genetic determinant for the expression of resistance to macrolides among methicillin-resistant Staphylococcus aureus clinical isolates in Greece. J Antimicrob Chemother. 2004; 53: 814-817.

Schmitz FJ, Sadurski R, Kray A, Boos M, Geisel R, Kohrer K, et al. Prevalence of macrolide-resistance genes in Staphylococcus aureus and Enterococcus faecium isolates from 24 European university hospitals. J Antimicrob Chemother. 2000; 45: 891-894.

Cetin ES, Gunes H, Kaya S, Aridogan BC, Demirci M. Distribution of genes encoding resistance to macrolides, lincosamides and streptogramins among clinical staphylococcal isolates in a Turkish university hospital. J Microbiol Immunol Infect. 2010; 43: 524-529.

Monecke S, Ehricht R. Rapid genotyping of methicillin-resistant Staphylococcus aureus (MRSA) isolates using miniaturised oligonucleotide arrays. Clin Microbiol Infect. 2005; 11: 825-833.

Kanj S, Whitelaw A, Dowzicky M. In vitro activity of tigecycline and comparators against Gram-positive and Gram-negative isolates collected from the Middle East and Africa between 2004 and 2011. Int J Antimicrob Agents. 2014; 43: 170–178.







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