Health Review: Mutational Changes

Introduction

The well-defined group is L. acidophilus, dividing into Lactobacillus phylogenetic subgroups. Its classification, although moderately built by DNA-DNA homology, shows a 32% to 50% GC content existing in genomic species (Felis & Dellaglio, 2007). Among the ephemeral and permanent residents of normal gut flora, Lactobacillus acts as a reservoir of antibiotic resistance genes and offers a model place for parallel gene transfer (Devirgiliis et al., 2011). E. coli has the capability to colonize different anatomical sites due in part to genome plasticity and transformation through the gain or loss of genetic material, which influences its resistance or virulence. Therefore, horizontal gene transfer remains an important factor in the adaptation and evolution of E. coli to different niches (Ahmed et al., 2008; Mellata et al., 2010).

Health Review: Mutational Changes

UPEC strains can trigger acute infections and recurrent infections that do not respond to common antimicrobial treatments. ß-lactam antibiotics, fluoroquinolones, or trimethoprim/sulfamethoxazole are generally included in UTI treatment (Chulain et al., 2005; Johnson et al., 2004; Molina-López et al., 2011). According to Johnson (2000), treatment depends on patient age, sex, pathogen involvement, the course of disease, and the urinary tract's anatomic areas. The influence of resistance may be associated with variations in the bacterial genome by acquisition, mutation, or horizontal transmission of extrachromosomal or chromosomal material (Moura et al., 2009; Backer et al., 2008; Hong et al., 2009).

Random antibiotic resistance can occur due to some mutations. These mutations are the result of errors during DNA replication or disorganization in the repair mechanisms of DNA damage during bacterial cell division and are recognized as natural mutations. A few changes at seven positions of the gyrA gene and in three positions of the parC gene in Escherichia coli result in a quinolone-resistant phenotype. Mechanisms of antibiotic resistance involving efflux or import systems are genetically determined by mutations in regulatory regions of genes and even in promoter regions known as multidrug resistance (MDR) efflux pumps (Piddock, 2006; Depardieu et al., 2007).

Certain changes occur in non-dividing cells or in cells that have a low rate of division and are related to non-lethal selection pressure that favors bacterial cells. Such mutations are named adaptive and represent the main source of the emergence of antibiotic-resistant phenotypes in natural conditions. DNA polymerase V prone-errors (umuCD) and DNA polymerase IV (dinB), which increase the rate of mutations transiently, are the main points in these processes. Enhancing the rate of occurrence of antibiotic-resistant phenotypes of Escherichia coli, some antibiotics are capable of producing bacterial DNA damage and triggering the mutagenic SOS response. Accumulation of single-stranded DNA because of lesions that block replication of the bacterial chromosome leads to the formation of RecA nucleoprotein complexes. A required step for assembling mutagen-dependent DNA polymerase V UmuD'2C is another role of coprotease RecA is to process UmuD to UmuD'. This allows DNA replication to continue, albeit at the cost of fidelity and the introduction of mutations (Rosche & Foster, 2000; Sutton et al., 2000; Bjedov et al., 2003; Janion, 2008).

Mechanisms of Antibiotic Resistance

Escherichia coli cells, known as MarA, Sox, and Rob, activate a set of 40 promoters belonging to the marA/soxS/rob regulon, which are some transcription factors whose function includes antibiotic resistance. Multiple antibiotic resistance is inherently determined by the locus mar, located at 34 minutes on the chromosome of Escherichia coli, by monitoring the intrinsic exposure of these bacterial strains. Four genes, marC, marR, marA, and marB, present in the MarCRAB locus, are arranged in two transcriptional units. Escherichia coli responds to oxidative stress and the action of weak acids. In fact, the first promoter initiated by MarA is the marRAB promoter, which increases their own synthesis. MarR inactivation by mutations or small molecules activates marRAB transcription and determines the duration of the antibiotic resistance phenotype (Barbosa et al., 2000; Alekshun et al., 2004).

Quinolone Resistance

Mutational changes in the FQ target enzymes, namely, DNA topoisomerase II (DNA gyrase) and topoisomerase IV, are recognized as major mechanisms through which resistance develops in Escherichia coli. The quinolone resistance-determining regions (QRDRs) in FQ-resistant isolates contain mutational hot spots localized in defined regions. The primary target in Gram-negative bacteria, in isolates displaying FQ resistance, DNA gyrase, commonly presents substitutions at amino acid position Ser83 and/or Asp87 of the GyrA subunit, whereas substitutions at residues Ser80 and Glu84 are commonly identified alterations in the ParC subunit of the topoisomerase IV (Heisig, 1996; Ozeki et al., 1997). According to Hopkins et al. (2005) and Strahilevitz et al. (2009), mutations in the quinolone target genes are required to achieve a clinical level of resistance, but other mechanisms may also contribute to quinolone/FQ resistance. These include decreased uptake of the drug due to the loss of a membrane-bound porin; drug extrusion via efflux pumps, some of which may have a broad substrate specificity; or one of the further described plasmid-mediated quinolone resistance (PMQR) mechanisms.