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Antimicrobial resistance (AMR) is a global health threat requiring urgent attention and effective strategies for containment. AMR is fueled by wastewater mismanagement and global mobility, disseminating multidrug-resistant (MDR) strains worldwide. While global estimates of AMR burden have been informative, community-level understanding has received little attention despite reports of high AMR prevalence in healthy communities. We assessed the "invasion" of antibiotic resistance genes (ARGs) into the normal human flora by characterizing AMR Escherichia coli in local wastewaters contributed by a healthy youth population. This study estimated 26% (out of 300 isolates) resistant and 59% plasmid-bearing E. coli in local wastewater. Of the 78 AMR isolates, the frequency of mono-resistance was higher against tetracycline (32%), followed by kanamycin (17%) and chloramphenicol (9%). Five isolates were potentially MDR. We further sequenced four MDRs and four sensitive strains to comprehend the genome and resistome diversity in comparison to the global wastewater E. coli (genomes from the PATRIC database). The whole-genome analysis revealed extensive genome similarity among global isolates, suggesting global dissemination and colonization of E. coli. Global wastewater resistome majorly comprised ARGs against aminoglycosides (26%), beta-lactam (17%), sulfonamide (11%), and trimethoprim (8%). Resistance to colistin, a last-resort antibiotic, was prevalent in MDRs of European and South Asian isolates. A systems approach is required to address the AMR crisis on a global scale, reduce antibiotic usage, and increase the efficiency of wastewater management and disinfection. [ABSTRACT FROM AUTHOR]

Toxin-antitoxin (TA) systems consist of a bicistronic operon, encoding a toxin and an antitoxin. They are widely distributed in the prokaryotic kingdom, often in multiple numbers. TAs are implicated in contradicting phenomena of persistence and programmed cell death (PCD) in bacteria. mazEF TA system, one of the widely distributed type II toxin-antitoxin systems, is particularly implicated in PCD of Escherichia coli. Nutrient starvation, antibiotic stress, heat shock, DNA damage and other kinds of stresses are shown to elicit mazEF-mediated-PCD. ppGpp and extracellular death factor play a central role in regulating mazEF-mediated PCD. The activation of mazEF system is achieved through inhibition of transcription or translation of mazEF loci. Upon activation, MazF cleaves RNA in a ribosome-independent fashion and subsequent processes result in cell death. It is hypothesized that PCD aids in perseverance of the population during stress; the surviving minority of the cells can scavenge the nutrients released by the dead cells, a kind of 'nutritional-altruism.' Issues regarding the strains, reproducibility of experimental results and ecological plausibility necessitate speculation. We review the molecular mechanisms of the activation of mazEF TA system, the consequences leading to cell death and the pros and cons of the altruism hypothesis from an ecological perspective. [ABSTRACT FROM AUTHOR]