Antimicrobial Resistance Dynamics in Chilean Shigella sonnei Strains Within Two Decades: Role of Shigella Resistance Locus Pathogenicity Island and Class 1 and Class 2 Integrons.

Cecilia S Toro,Rossanna Camponovo,Juan Antonio Ugalde,Germán Hermosilla,María Teresa Ulloa,Janepsy Díaz,Tania Henríquez,Juan Carlos Salazar,Camila García,Leandro A Cádiz,David A Montero,Patricia Díaz

doi:10.3389/fmicb.2021.794470

Abstract

Shigellosis is an enteric infectious disease in which antibiotic treatment is effective, shortening the duration of symptoms and reducing the excretion of the pathogen into the environment. Shigella spp., the etiologic agent, are considered emerging pathogens with a high public health impact due to the increase and global spread of multidrug-resistant (MDR) strains. Since Shigella resistance phenotype varies worldwide, we present an overview of the resistance phenotypes and associated genetic determinants present in 349 Chilean S. sonnei strains isolated during the periods 1995–1997, 2002–2004, 2008–2009, and 2010–2013. We detected a great variability in antibiotic susceptibility patterns, finding 300 (86%) MDR strains. Mobile genetic elements (MGE), such as plasmids, integrons, and genomic islands, have been associated with the MDR phenotypes. The Shigella resistance locus pathogenicity island (SRL PAI), which encodes for ampicillin, streptomycin, chloramphenicol, and tetracycline resistance genes, was detected by PCR in 100% of the strains isolated in 2008–2009 but was less frequent in isolates from other periods. The presence or absence of SRL PAI was also differentiated by pulsed-field gel electrophoresis. An atypical class 1 integron which harbors the blaOXA–1-aadA1-IS1 organization was detected as part of SRL PAI. The dfrA14 gene conferring trimethoprim resistance was present in 98.8% of the 2008–2009 isolates, distinguishing them from the SRL-positive strains isolated before that. Thus, it seems an SRL-dfrA14 S. sonnei clone spread during the 2008–2009 period and declined thereafter. Besides these, SRL-negative strains harboring class 2 integrons with or without resistance to nalidixic acid were detected from 2011 onward, suggesting the circulation of another clone. Whole-genome sequencing of selected strains confirmed the results obtained by PCR and phenotypic analysis. It is highlighted that 70.8% of the MDR strains harbored one or more of the MGE evaluated, while 15.2% lacked both SRL PAI and integrons. These results underscore the temporal dynamics of antimicrobial resistance in S. sonnei strains circulating in Chile, mainly determined by the spread of MGE conferring MDR phenotypes. Since shigellosis is endemic in Chile, constant surveillance of antimicrobial resistance phenotypes and their genetic basis is a priority to contribute to public health policies.

Highlights

Shigellosis is one of the most common diarrheal diseases in children under 5 years old, especially in developing countries, it occurs in people of all ages worldwide (Kotloff et al, 2018)
To better understand the temporal dynamics of antibiotic resistance of these strains, they were grouped according to the date of isolation in periods A–E
Antimicrobial susceptibility test (AST) for all these 349 strains showed that 100% were sensitive to ciprofloxacin, while 3 (0.9%) and 33 (9.5%) isolates were resistant to cefotaxime and nalidixic acid, respectively

Summary

Introduction

Shigellosis is one of the most common diarrheal diseases in children under 5 years old, especially in developing countries, it occurs in people of all ages worldwide (Kotloff et al, 2018). Shigella spp., the etiologic agent, are considered emerging pathogens with a high public health impact due to the increase and global spread of multidrug-resistant (MDR) strains (Chu et al, 1998; Ashkenazi et al, 2003; Vrints et al, 2009; Shiferaw et al, 2012; Gu et al, 2017; Puzari et al, 2018) This situation is worrying because shigellosis is one of the few enteric infections for which antibiotics are recommended as therapeutic management (Williams and Berkley, 2016, 2018). The emergence of Shigella spp. resistant to the most commonly used antibiotics for treating this disease is reported in Latin America, North America, Europe, and South Asia (Chu et al, 1998; Oh et al, 2003; Gu et al, 2012; Shiferaw et al, 2012; Marcoleta et al, 2013; Puzari et al, 2018; Chung The et al, 2019, 2021; Sati et al, 2019; Bardsley et al, 2020)

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