<p><em>Shigella</em>: Antibiotic-Resistance Mechanisms And New Horizons For Treatment</p>

Abstract

Shigella spp. are a common cause of diarrheal disease and have remained an important pathogen responsible for increased rates of morbidity and mortality caused by dysentery each year around the globe. Antibiotic treatment of Shigella infections plays an essential role in reducing prevalence and death rates of the disease. However, treatment of these infections remains a challenge, due to the global rise in broad-spectrum resistance to many antibiotics. Drug resistance in Shigella spp. can result from many mechanisms, such as decrease in cellular permeability, extrusion of drugs by active efflux pumps, and overexpression of drug-modifying and -inactivating enzymes or target modification by mutation. Therefore, there is an increasing need for identification and evolution of alternative therapeutic strategies presenting innovative avenues against Shigella infections, as well as paying further attention to this infection. The current review focuses on various antibiotic-resistance mechanisms of Shigella spp. with a particular emphasis on epidemiology and new mechanisms of resistance and their acquisition, and also discusses the status of novel strategies for treatment of Shigella infection and vaccine candidates currently under evaluation in preclinical or clinical phases.

NAIP–NLRC4-deficient mice are susceptible to shigellosis

“…Disease symptoms include fever, abdominal cramping, and inflammatory diarrhea characterized by the presence of neutrophils and, in severe cases, blood ( Kotloff et al, 2018 ). There is no approved vaccine for Shigella and antibiotic resistance continues to rise ( Ranjbar and Farahani, 2019 ). Shigella pathogenesis is believed to be driven by bacterial invasion, replication, and spread within colonic intestinal epithelial cells (IECs).…”

Adaptation of a fluoroquinolone-sensitiveShigella sonneito norfloxacin exposure

“…resistance genes are often of plasmid origins, such as plasmid-mediated quinolone resistance (PMQR) genes namely qnr, or extended spectrum beta-lactamase (ESBLs)(Ranjbar & Farahani 2019). Other than that, phage profiling by PHASTER(Arndt et al 2016) showed 17 prophage regions, including 10 intact regions (Figure 1a).…”

Antimicrobial resistance in enteric bacteria: current state and next-generation solutions

“…51 The genus Shigella contains bacteria closely related to E. coli and is comprised of four major pathogenic species: S. dysenteriae, S. flexneri, S. boydii, and S. sonnei. 21 Shigella can be transmitted from person-to-person, or through contaminated food sources and water ( Figure 1a), while some AMR Shigella outbreaks are associated with international travel and sexual transmission. 57 Shigella infections were once highly responsive to cheaper antibiotics such as β-lactams and antifolates, but rising resistance rates have shifted the treatments of choice toward macrolides or fluoroquinolones, with ceftriaxone as an alternative treatment option.…”

“…50 MDR Shigella can arise through plasmid-borne or integron-mobilized elements encoding multiple types of resistance. 21,54 A commonly observed MDR phenotype includes resistance to ampicillin, chloramphenicol, streptomycin, sulfonamides, and tetracyclines (ACSSuT). 21,24,58 Epidemics driven by MDR Shigella have risen worldwide within the last decade and requires significant intervention efforts to prevent further disease.…”