Deciphering the genetic network and programmed regulation of antimicrobial resistance in bacterial pathogens

Abstract

Antimicrobial resistance (AMR) in bacteria is an important global health problem affecting humans, animals, and the environment. AMR is considered as one of the major components in the “global one health”. Misuse/overuse of antibiotics in any one of the segments can impact the integrity of the others. In the presence of antibiotic selective pressure, bacteria tend to develop several defense mechanisms, which include structural changes of the bacterial outer membrane, enzymatic processes, gene upregulation, mutations, adaptive resistance, and biofilm formation. Several components of mobile genetic elements (MGEs) play an important role in the dissemination of AMR. Each one of these components has a specific function that lasts long, irrespective of any antibiotic pressure. Integrative and conjugative elements (ICEs), insertion sequence elements (ISs), and transposons carry the antimicrobial resistance genes (ARGs) on different genetic backbones. Successful transfer of ARGs depends on the class of plasmids, regulons, ISs proximity, and type of recombination systems. Additionally, phage-bacterial networks play a major role in the transmission of ARGs, especially in bacteria from the environment and foods of animal origin. Several other functional attributes of bacteria also get successfully modified to acquire ARGs. These include efflux pumps, toxin-antitoxin systems, regulatory small RNAs, guanosine pentaphosphate signaling, quorum sensing, two-component system, and clustered regularly interspaced short palindromic repeats (CRISPR) systems. The metabolic and virulence state of bacteria is also associated with a range of genetic and phenotypic resistance mechanisms. In spite of the availability of a considerable information on AMR, the network associations between selection pressures and several of the components mentioned above are poorly understood. Understanding how a pathogen resists and regulates the ARGs in response to antimicrobials can help in controlling the development of resistance. Here, we provide an overview of the importance of genetic network and regulation of AMR in bacterial pathogens.

Antimicrobial Resistance Genes in Respiratory Bacteria from Weaned Dairy Heifers

“…Various factors [ 72 , 73 ] are important for the expression of AMR genes, which may not be accurately reflected in culture and susceptibility testing conditions. Susceptibility testing may determine the in vitro susceptibility of the isolate at the time of sampling, but does not demonstrate the full AMR potential of the isolate.…”

Antimicrobial resistance and mechanisms of epigenetic regulation

“…NAPs form numerous aggregated structures with bacterial genomic DNA and participate in processes such as replication, separation, translation, and repair of prokaryotic genomic DNA. Among the primary NAPs studied are histone‐like protein (HU), leucine-responsive regulatory protein (Lrp), virulence factor transcriptional regulator (Mga Spn ) and Histone-like nucleoid-structuring (H-NS) ( Casadesús and Low, 2006 ; Xiao et al., 2021 ; Ziegler and Freddolino, 2021 ; Ramamurthy et al., 2022 ; Stojkova and Spidlova, 2022 ).…”

The impact of antibiotic exposure on antibiotic resistance gene dynamics in the gut microbiota of inflammatory bowel disease patients

“… Jiang et al (2017) provided evidence for the transfer of ARGs from actinobacteria to proteobacteria. Under the pressure of antibiotics, HGT fosters genomic diversity and rapid adaptation in bacteria ( Ramamurthy et al, 2022 ). Antibiotics can amplify the dissemination of ARGs among gut bacterial communities, with profound and lasting impacts on microbial composition ( Jutkina et al, 2016 ; Dhariwal et al, 2023 ).…”