Determination of capsular serotypes, antibiotic susceptibility pattern, and molecular mechanism of erythromycin resistance among clinical isolates of Group B Streptococcus in Isfahan, Iran

Motallebirad, Tahereh; Fazeli, Hossein; Azadi, Davood; Shokri, Dariush; Moghim, Sharareh; Esfahani, Bahram Nasr

Determination of capsular serotypes, antibiotic susceptibility pattern, and molecular mechanism of erythromycin resistance among clinical isolates of Group B Streptococcus in Isfahan, Iran

Authors

¹ Department of Bacteriology and Virology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

² Department of Basic and Laboratory Sciences, Khomein University of Medical Sciences, Khomein, Iran

³ Infectious Disease and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Documented streptococcal resistance to erythromycin has recently been raised. The aim of this study is to identify the molecular mechanism of erythromycin resistance among group B Streptococcus (GBS) strains and to correlate with the clinical origin of strains. Materials and Methods: A total number of 134 colonizing (n = 36), invasive (n = 36), noninvasive (n = 46), and asymptomatic (n = 16) GBS isolates were characterized by the detection of dltS gene, capsular serotyping, antibiotic susceptibility profiles using disc diffusion method, and screening of the ermB, ermTR, and mefA resistance genes. Results: The distribution of capsular serotypes was as follow: serotype III (24.6%), Ia (21.6%), V (17.9%), Ib (14.9%), II (8.9%), IV (8.9%), VI (1.5%), and VII (1.5%). From 134 GBS isolates, 51 (38%) isolates were resistant to erythromycin. The constitutive macrolide lincosamide streptogrmin B (MLSB) was the most common resistance phenotype (62.7%), followed by inducible MLSB (27.4%) and M phenotype (9.8%). Erythromycin resistance rate was higher among asymptomatic GBS strains (13/16, 81.2%). Serotype III was the most prevalent type among resistant isolates (41.1%). The ermB gene highly distributed among resistant strains (64.7%), followed by ermTR (21.5%) and mefA (9.8%). The ermB gene was related to constitutive MLSB phenotype (84.3%, P < 0.05) and serotypes III (61.9%), Ib (87.5%), and V (83.3%). All M phenotype strains harbored mefA gene and were in association with serotype Ia (90%). Conclusion: The current study suggests that ribosomal modification with erm genes is the main mechanism of erythromycin resistance. Because of relatively high prevalence of erythromycin resistance, double disc test highly recommended for GBS disease treatment and intrapartum prophylaxis among penicillin intolerant patients in our region.

Keywords

References

1.	Shabayek S, Spellerberg B. Group B streptococcal colonization, molecular characteristics, and epidemiology. Front Microbiol 2018;9:437.
2.	Madrid L, Seale AC, Kohli-Lynch M, Edmond KM, Lawn JE, Heath PT, et al. Infant group B streptococcal disease incidence and serotypes worldwide: Systematic review and meta-analyses. Clin Infect Dis 2017;65:S160-72.
3.	Steer PJ, Russell AB, Kochhar S, Cox P, Plumb J, Gopal Rao G. Group B streptococcal disease in the mother and newborn – A review. Eur J Obstet Gynecol Reprod Biol 2020;252:526-33.
4.	Pietrocola G, Arciola CR, Rindi S, Montanaro L, Speziale P. Streptococcus agalactiae non-pilus, cell wall-anchored proteins: involvement in colonization and pathogenesis and potential as vaccine candidates. Front Immunol 2018;9:602.
5.	Furfaro LL, Chang BJ, Payne MS. Perinatal streptococcus agalactiae epidemiology and surveillance targets. Clin Microbiol Rev 2018;31:e00049-e00018.
6.	Seki T, Kimura K, Reid ME, Miyazaki A, Banno H, Jin W, et al. High isolation rate of MDR group B streptococci with reduced penicillin susceptibility in Japan. J Antimicrob Chemother 2015;70:2725-8.
7.	Hayes K, O'Halloran F, Cotter L. A review of antibiotic resistance in Group B Streptococcus: The story so far. Crit Rev Microbiol 2020;46:1-17.
8.	Oppegaard O, Skrede S, Mylvaganam H, Kittang BR. Emerging threat of antimicrobial resistance in β-hemolytic streptococci. Front Microbiol 2020;11:797.
9.	Poyart C, Tazi A, Réglier-Poupet H, Billoët A, Tavares N, Raymond J, et al. Multiplex PCR assay for rapid and accurate capsular typing of group B streptococci. J Clin Microbiol 2007;45:1985-8.
10.	Mobasherizadeh S, Shojaei H, Azadi D, Havaei SA, Rostami S. Molecular characterization and genotyping of methicillin-resistant Staphylococcus aureus in nasal carriage of healthy Iranian children. J Med Microbiol 2019;68:374-8.
11.	Ogbolu DO, Alli OA, Oluremi AS, Onifade CO. Erythromycin resistance determinants in clinical gram positive cocci isolated from Nigerian patients. J Clin Diagn Res 2018;12:5-10.
12.	Seale AC, Bianchi-Jassir F, Russell NJ, Kohli-Lynch M, Tann CJ, Hall J, et al. Estimates of the burden of group B streptococcal disease worldwide for pregnant women, stillbirths, and children. Clin Infect Dis 2017;65:S200-19.
13.	Khademi F, Sahebkar A. Group B Streptococcus drug resistance in pregnant women in Iran: A meta-analysis. Taiwan J Obstet Gynecol 2020;59:635-42.
14.	Jalalifar S, Havaei SA, Motallebirad T, Moghim S, Fazeli H, Esfahani BN. Determination of surface proteins profile, capsular genotyping, and antibiotic susceptibility patterns of Group B Streptococcus isolated from urinary tract infection of Iranian patients. BMC Res Notes 2019;12:1-6.
15.	Khodaei F, Najafi M, Hasani A, Kalantar E, Sharifi E, Amini A, et al. Pilus–encoding islets in S. agalactiae and its association with antibacterial resistance and serotype distribution. Microb Pathogen 2018;116:189-94.
16.	Bergal A, Loucif L, Benouareth DE, Bentorki AA, Abat C, Rolain JM. Molecular epidemiology and distribution of serotypes, genotypes, and antibiotic resistance genes of Streptococcus agalactiae clinical isolates from Guelma, Algeria and Marseille, France. Eur J Clin Microbiol Infect Dis 2015;34:2339-48.
17.	López Y, Parra E, Cepas V, Sanfeliú I, Juncosa T, Andreu A, et al. Serotype, virulence profile, antimicrobial resistance and macrolide-resistance determinants in Streptococcus agalactiae isolates in pregnant women and neonates in Catalonia, Spain. Enferm Infecc Microbiol Clin 2018;36:472-7.
18.	Borchardt SM, DeBusscher JH, Tallman PA, Manning SD, Marrs CF, Kurzynski TA, et al. Frequency of antimicrobial resistance among invasive and colonizing Group B streptococcal isolates. BMC Infect Dis 2006;6:57.
19.	Sadowy E, Matynia B, Hryniewicz W. Population structure, virulence factors and resistance determinants of invasive, non-invasive and colonizing Streptococcus agalactiae in Poland. J Antimicrob Chemother 2010;65:1907-14.
20.	Bianchi-Jassir F, Paul P, To KN, Carreras-Abad C, Seale AC, Jauneikaite E, et al. Systematic review of Group B Streptococcal capsular types, sequence types and surface proteins as potential vaccine candidates. Vaccine 2020;38:6682-94.
21.	Song JY, Lim JH, Lim S, Yong Z, Seo HS. Progress toward a group B streptococcal vaccine. Hum Vaccin Immunother 2018;14:2669-81.
22.	Mansouri S, Ghasami E, Shahabi Najad N. Vaginal colonization of group B streptococci during late pregnancy in southeast of Iran: Incidence, serotype distribution and susceptibility to antibiotics. J Med Sci 2008;8:574-8.
23.	Beigverdi R, Jabalameli F, Mirsalehian A, Hantoushzadeh S, Boroumandi S, Taherikalani M, et al. Virulence factors, antimicrobial susceptibility and molecular characterization of Streptococcus agalactiae isolated from pregnant women. Acta Microbiol Immunol Hung 2014;61:425-34.
24.	Nabavinia M, Khalili MB, Eslami G, Vakili M, Azartoos N, Mojibiyan M. Distribution of Pilus island and antibiotic resistance genes in Streptococcus agalactiae obtained from vagina of pregnant women in Yazd, Iran. Iran J Microbiol 2020;12:411-6.
25.	Jannati E, Roshani M, Arzanlou M, Habibzadeh S, Rahimi G, Shapuri R. Capsular serotype and antibiotic resistance of group B streptococci isolated from pregnant women in Ardabil, Iran. Iran J Microbiol 2012;4:130-5.
26.	Lu B, Chen X, Wang J, Wang D, Zeng J, Li Y, et al. Molecular characteristics and antimicrobial resistance in invasive and noninvasive Group B Streptococcus between 2008 and 2015 in China. Diagn Microbiol Infect Dis 2016;86:351-7.
27.	Wu B, Su J, Li L, Wu W, Wu J, Lu Y, et al. Phenotypic and genetic differences among group B Streptococcus recovered from neonates and pregnant women in Shenzhen, China: 8-year study. BMC Microbiol 2019;19:185.
28.	Cattoir V., Leclercq R. Resistance to Macrolides, Lincosamides, and Streptogramins. In: Mayers D., Sobel J., Ouellette M., Kaye K., Marchaim D. (eds) Antimicrobial Drug Resistance. Springer, Cham. 2017;269-80.
29.	Gizachew M, Tiruneh M, Moges F, Adefris M, Tigabu Z, Tessema B. Streptococcus agalactiae from Ethiopian pregnant women; prevalence, associated factors and antimicrobial resistance: Alarming for prophylaxis. Ann Clin Microbiol Antimicrob 2019;18:3.
30.	Akdoğan Kittana FN, Mustak IB, Hascelik G, Saricam S, Gurler N, Diker KS. Erythromycin-resistant Streptococcus pneumoniae: Phenotypes, genotypes, transposons and pneumococcal vaccine coverage rates. J Med Microbiol 2019;68:874-81.

Advanced Biomedical Research