Antimicrobial Resistance in Shigella Species and Public Health Implications

Shigella spp. are a leading cause of bacillary dysentery worldwide, disproportionately affecting children in low-income countries but increasingly reported in high-income settings. The rise of antimicrobial resistance (AMR) in Shigella flexneri and Shigella sonnei has undermined first-line treatments, including fluoroquinolones, macrolides and third-generation cephalosporins. Resistance mechanisms often involve plasmid-encoded extended-spectrum β-lactamases, macrolide acetyltransferases and mutations in chromosomal quinolone targets. Horizontal gene transfer via conjugative plasmids accelerates the dissemination of resistance determinants across serotypes and geographical regions. This has led to outbreaks of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains in community and clinical settings, including sexual networks among men who have sex with men. AMR in Shigella presents substantial challenges to public health, necessitating robust laboratory surveillance, stewardship of existing antibiotics and development of novel therapeutics and vaccines. Enhanced genomic monitoring informs outbreak response and guides empiric therapy, while improving water, sanitation and hygiene practices remains essential to reduce transmission.

Research from Nature Portfolio

A genomic study of Shigella sonnei isolates in France between 2005 and 2021 revealed a sharp rise in strains resistant to ciprofloxacin, third-generation cephalosporins and azithromycin from 2015 onward. Analysis of 164 extensively drug-resistant isolates identified multiple clusters within a ciprofloxacin-resistant lineage that was originally selected in South Asia. Subsequent acquisition of macrolide and β-lactam resistance genes through diverse plasmid backbones, including IncFII and IncI1, highlighted the complex evolutionary pathways leading to XDR phenotypes. The findings underscore the need for continuous genome-based surveillance to detect emergent resistance patterns and guide public health action.

A foundational investigation into the role of horizontal gene transfer demonstrated that repeated mobilisation of a single resistance plasmid among different Shigella species amplified epidemic spread, particularly in sexual transmission networks. Parallel outbreaks driven by plasmid exchange contrasted sharply with slower expansions of chromosomally mediated resistance, emphasising the epidemiological impact of conjugative elements on the global burden of AMR.

Antimicrobial Resistance in Shigella Species and Public Health Implications publication trend

The graph below shows the total number of articles in antimicrobial resistance in shigella species and public health implications across all publications each year (not limited to Nature Index journals).

Technical terms

Multidrug-resistant (MDR): Bacteria resistant to three or more classes of antimicrobial agents.

Extensively drug-resistant (XDR): Bacteria resistant to at least one agent in all but two or fewer antimicrobial categories.

Plasmid: Extrachromosomal DNA molecule capable of autonomous replication and horizontal transfer of resistance genes.

Extended-spectrum β-lactamase (ESBL): Enzymes that hydrolyse a wide range of β-lactam antibiotics, including third-generation cephalosporins.

Whole-genome sequencing (WGS): Laboratory method that determines the complete DNA sequence of an organism’s genome, facilitating detailed surveillance of resistance determinants.

References

1. Emergence of extensively drug-resistant and multidrug-resistant Shigella flexneri serotype 2a associated with sexual transmission among gay, bisexual, and other men who have sex with men, in England: a descriptive epidemiological study. The Lancet Infectious Diseases (2023).
2. Rapid emergence of extensively drug-resistant Shigella sonnei in France. Nature Communications (2023).
3. The re-emergence of sexually transmissible multidrug resistant Shigella flexneri 3a, England, United Kingdom. npj Antimicrobials and Resistance (2024).
4. Twenty-five years of sentinel laboratory-based surveillance of shigellosis in a high-income country endemic for the disease, Israel, 1998 to 2022. Eurosurveillance (2024).
5. Horizontal antimicrobial resistance transfer drives epidemics of multiple Shigella species. Nature Communications (2018).