Genetic Basis Of Antibiotic Resistance Research Articles

Unraveling the genetic basis of antibiotic resistance in Staphylococcus aureus: Focus on mecA and PVL Genes

Background Staphylococcus aureus infections, including Methicillin-Resistant S. aureus (MRSA) and Methicillin-Sensitive S. aureus (MSSA), present significant challenges in healthcare due to rising antimicrobial resistance. This study evaluates the genetic basis of antibiotic resistance in S. aureus, focusing on key resistance-associated genes mecA and PVL. Methods A total of 568 clinical specimens were analyzed for the presence of S. aureus. Demographic data were collected to assess age-dependent prevalence. Antimicrobial susceptibility testing was conducted to evaluate resistance patterns. The prevalence of the mecA and PVL genes was determined using molecular techniques. Results S. aureus was identified in 37.9% of cases, with the highest prevalence (60-79 age group). All S. aureus isolates showed 100% resistance to penicillin. Multidrug-resistant (MDR) strains accounted for 84.19% of isolates, with a significant presence of extensively drug-resistant (XDR) strains. The mecA gene was prevalent in 82.79% of MRSA isolates, indicating its strong association with methicillin resistance. Additionally, 41.86% of all S. aureus isolates were positive for the PVL gene, highlighting its widespread distribution. Conclusions The high prevalence of mecA and PVL genes in S. aureus strains underscores the challenges in managing these infections. These findings emphasize the necessity for judicious antibiotic use and enhanced collaborative efforts to combat antimicrobial resistance. Understanding the genetic basis of resistance can inform more effective diagnostic, therapeutic, and preventive strategies, ultimately improving patient outcomes in S. aureus infections.

Unraveling the genetic basis of antibiotic resistance in Staphylococcus aureus: Focus on mecA and PVL Genes

Background Staphylococcus aureus infections, including Methicillin-Resistant S. aureus (MRSA) and Methicillin-Sensitive S. aureus (MSSA), present significant challenges in healthcare due to rising antimicrobial resistance. This study evaluates the genetic basis of antibiotic resistance in S. aureus, focusing on key resistance-associated genes mecA and PVL. Methods A total of 568 clinical specimens were analyzed for the presence of S. aureus. Demographic data were collected to assess age-dependent prevalence. Antimicrobial susceptibility testing was conducted to evaluate resistance patterns. The prevalence of the mecA and PVL genes was determined using molecular techniques. Results S. aureus was identified in 37.9% of cases, with the highest prevalence (60-79 age group). All S. aureus isolates showed 100% resistance to penicillin. Multidrug-resistant (MDR) strains accounted for 84.19% of isolates, with a significant presence of extensively drug-resistant (XDR) strains. The mecA gene was prevalent in 82.79% of MRSA isolates, indicating its strong association with methicillin resistance. Additionally, 41.86% of all S. aureus isolates were positive for the PVL gene, highlighting its widespread distribution. Conclusions The high prevalence of mecA and PVL genes in S. aureus strains underscores the challenges in managing these infections. These findings emphasize the necessity for judicious antibiotic use and enhanced collaborative efforts to combat antimicrobial resistance. Understanding the genetic basis of resistance can inform more effective diagnostic, therapeutic, and preventive strategies, ultimately improving patient outcomes in S. aureus infections.

Genetic Characterization of Extended-Spectrum Beta-Lactamase (ESBL) and Metallo-Beta-Lactamase (MBL) Producing Klebsiella pneumoniae from Diabetic Foot Ulcer (DFU)

ABSTRACT Background: Antibiotic resistance in common pathogenic bacteria is linked with the genetic makeup. The genetic basis of antibiotic resistance may vary in different species or pathophysiological conditions. Objectives: We studied the antibiotic resistance in Klebsiella pneumonia isolates from DFU in the western Indian population. We also studied the presence of ESBL and MBL mechanisms of antibiotic resistance along with the prevalence of the genes involved in ESBL (TEM ESBL , SHV ESBL , and CTX-M ESBL ) and MBL (NDM-1 bla , KPC bla , OXA-48 bla , and VIM bla ) production. Results: A total of 161 K. pneumoniae isolates were analyzed; among which 50.93% were positive for ESBL and 45.96% were positive for MBL production. Most of the isolates were resistant to antibiotics used in the present study and partially resistant to Imipenem and Amikacin. There was no relation between the antibiotic resistance of the isolates and the production of ESBL or MBL mechanism of antibiotic resistance. Further, TEM ESBL was the most prevalent gene in K. pneumoniae isolates followed by CTX-M ESBL , NDM-1 bla , SHV ESBL , and KPC bla . VIM bla was the least prevalent gene found in K. pneumoniae isolates. There was no difference in the prevalence of the genes with respect to the presence or absence of ESBL and MBL mechanism of resistance. Further, there was no relation between the prevalence of the genes and antibiotic resistance in K. pneumoniae isolates. Conclusion: These results along with the literature review suggest that the prevalence of the genes involved in antibiotic resistance mechanisms are widespread in India and their distribution varies in different studies.

Molecular Analysis of Pseudomonas aeruginosa Isolates with Mutant gyrA Gene and Development of a New Ciprofloxacin Derivative for Antimicrobial Therapy.

This study focuses on the prevalence of Pseudomonas aeruginosa in various medical specimens. In addition, the investigates of this research shows the genetic analysis of pathogen-resistant isolates and chemical modifications to ciprofloxacin. A total of 225 specimens from men and women aged 30 to 60 were carefully collected and examined, including samples from wound, burn, urine, sputum, and ear samples. The data were obtained from AL Muthanna hospitals. PCR-RFLP and gene expression analysis were used to identify resistant strains and explore the genetic basis of antibiotic resistance. A ciprofloxacin derivative was synthesized and confirmed through FT-IR, 1H-NMR, and mass spectroscopy techniques then it was tested as antibacterial agent. Also, molecular docking study was conducted to predict the mechanism of action for the synthesized derivative. The results demonstrated that wound samples had the highest positive rate (33.7%) of P. aeruginosa isolates. The PCR-RFLP testing correlated ciprofloxacin resistance with gyrA gene mutation. Gene expression analysis revealed significant changes in the gyrA gene expression in comparison to the reference rpsL gene subsequent to exposure to the synthesized derivative. Furthermore, the molecular docking investigation illustrated the strategic positioning of the ciprofloxacin derivative within the DNA-binding site of the gyrA enzyme. The examination of genetic expression patterns manifested diverse effects attributed to the CIP derivative on P. aeruginosa, thus portraying it as a viable candidate in the quest for the development of novel antimicrobial agents. Ciprofloxacin derivative may offer new antimicrobial therapeutic options for treating Pseudomonas aeruginosa infections in wound specimens, addressing resistance and gyrA gene mutations.

Clinical Resistant Strains of Enterococci and Their Correlation to Reduced Susceptibility to Biocides: Phenotypic and Genotypic Analysis of Macrolides, Lincosamides, and Streptogramins.

Enterococci are troublesome nosocomial, opportunistic Gram-positive cocci bacteria showing enhanced resistance to many commonly used antibiotics. This study aims to investigate the prevalence and genetic basis of antibiotic resistance to macrolides, lincosamides, and streptogramins (MLS) in Enterococci, as well as the correlation between MLS resistance and biocide resistance. From 913 clinical isolates collected from King Khalid Hospital, Hail, Saudi Arabia, 131 isolates were identified as Enterococci spp. The susceptibility of the clinical enterococcal isolates to several MLS antibiotics was determined, and the resistance phenotype was detected by the triple disk method. The MLS-involved resistance genes were screened in the resistant isolates. The current results showed high resistance rates to MLS antibiotics, and the constitutive resistance to all MLS (cMLS) was the most prevalent phenotype, observed in 76.8% of resistant isolates. By screening the MLS resistance-encoding genes in the resistant isolates, the erythromycin ribosome methylase (erm) genes that are responsible for methylation of bacterial 23S rRNA were the most detected genes, in particular, ermB. The ereA esterase-encoding gene was the most detected MLS modifying-encoding genes, more than lnuA (adenylation) and mphC (phosphorylation). The minimum inhibitory concentrations (MICs) of commonly used biocides were detected in resistant isolates and correlated with the MICs of MLS antibiotics. The present findings showed a significant correlation between MLS resistance and reduced susceptibility to biocides. In compliance with the high incidence of the efflux-encoding genes, especially mefA and mefE genes in the tolerant isolates with higher MICs to both MLS antibiotics and biocides, the efflux of resistant isolates was quantified, and there was a significant increase in the efflux of resistant isolates with higher MICs as compared to those with lower MICs. This could explain the crucial role of efflux in developing cross-resistance to both MLS antibiotics and biocides.

Genomic Analysis of Antibiotic-Resistant Staphylococcus epidermidis Isolates From Clinical Sources in the Kwazulu-Natal Province, South Africa.

Staphylococcus epidermidis has become an important nosocomial pathogen. Multidrug resistance makes S. epidermidis infections difficult to treat. The study aims to describe the genomic characteristics of methicillin-resistant S. epidermidis (MRSE) isolated from clinical sources, to comprehend the genetic basis of antibiotic resistance, virulence, and potential pathogenicity. Sixteen MRSE underwent whole-genome sequencing, and bioinformatics analyses were carried out to ascertain their resistome, virulome, mobilome, clonality, and phylogenomic relationships. In all, 75% of isolates displayed multidrug resistance and were associated with the carriage of multiple resistance genes including mecA, blaZ, tet(K), erm(A), erm(B), erm(C), dfrG, aac(6′)-aph(2′′), and cat(pC221) conferring resistance to β-lactams, tetracyclines, macrolide–lincosamide–streptogramin B, aminoglycosides, and phenicols, which were located on both plasmids and chromosomes. Their virulence profiles were evidenced by the presence of genes involved in adherence/biofilm formation (icaA, icaB, icaC, atl, ebh, and ebp), immune evasion (adsA, capC, and manA), and antiphagocytosis (rmlC, cdsA, and A). The community-acquired SCCmec type IV was the most common SCCmec type. The CoNS belonged to seven multilocus sequence types (MLSTs) and carried a diversity of mobile genetic elements such as phages, insertion sequences, and plasmids. The bacterial anti-phage defense systems clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR-Cas) immunity phage system and restriction-modification system (R-M system) and the arginine catabolic mobile element (ACME) involved in immune evasion and transport of virulence genes were also found. The insertion sequence, IS256, linked with virulence, was found in 56.3% of isolates. Generally, the isolates clustered according to STs, with some similarity but also considerable variability within isolates. Whole-genome sequencing and bioinformatics analysis provide insights into the likely pathogenicity and antibiotic resistance of S. epidermidis, necessitating surveillance of this emerging pathogen.

Genomic diversity of prevalent Staphylococcus epidermidis multidrug-resistant strains isolated from a Children's Hospital in México City in an eight-years survey.

Staphylococcus epidermidis is a human commensal and pathogen worldwide distributed. In this work, we surveyed for multi-resistant S. epidermidis strains in eight years at a children’s health-care unit in México City. Multidrug-resistant S. epidermidis were present in all years of the study, including resistance to methicillin, beta-lactams, fluoroquinolones, and macrolides. To understand the genetic basis of antibiotic resistance and its association with virulence and gene exchange, we sequenced the genomes of 17 S. epidermidis isolates. Whole-genome nucleotide identities between all the pairs of S. epidermidis strains were about 97% to 99%. We inferred a clonal structure and eight Multilocus Sequence Types (MLSTs) in the S. epidermidis sequenced collection. The profile of virulence includes genes involved in biofilm formation and phenol-soluble modulins (PSMs). Half of the S. epidermidis analyzed lacked the ica operon for biofilm formation. Likely, they are commensal S. epidermidis strains but multi-antibiotic resistant. Uneven distribution of insertion sequences, phages, and CRISPR-Cas immunity phage systems suggest frequent horizontal gene transfer. Rates of recombination between S. epidermidis strains were more prevalent than the mutation rate and affected the whole genome. Therefore, the multidrug resistance, independently of the pathogenic traits, might explain the persistence of specific highly adapted S. epidermidis clonal lineages in nosocomial settings.

Identification and Antibiotic Resistance Assessment of Ensifer adhaerens YX1, a Vitamin B12 -Producing Strain Used as a Food and Feed Additive.

This study provides phenotypic and molecular analyses of the antibiotic resistance of Ensifer adhaerens strain YX1 (CICC 11008s), a strain that was identified using a polyphasic taxonomy approach. The antibiotic resistance profile of E. adhaerens YX1 was assessed using the Clinical & Laboratory Standards Inst. (CLSI) method. The strain was susceptible to ciprofloxacin, levofloxacin, norfloxacin, ofloxacin, gentamicin, tobramycin, chloramphenicol, tetracycline, imipenem, and ceftazidime, and resistant to kanamycin, streptomycin, fosfomycin, and nitrofurantoin. The antibiotic resistance genes nsfA, nsfB, fosA, aph, and aadA1 were not detected in E. adhaerens YX1 via PCR using gene-specific primers. Subsequently, the genome sequence of E. adhaerens was screened for antibiotic genes. Although no antibiotic resistance genes were identified using the ResFinder database, five genes copies of one resistance gene, adeF, were detected using the Comprehensive Antibiotic Resistance Database (CARD). The results of this study will be useful for understanding the phenotypic and genotypic aspects of E. adhaerens antibiotic resistance. No safety issues were identified for E. adhaerens YX1 in terms of antibiotic resistance. Performing similar studies will be conducive to the safety assessment and control of the use of E. adhaerens in the food and feed industry. PRACTICAL APPLICATION: Few relevant reports are currently available regarding antibiotic resistance assessments or other safety evaluations for Ensifer adhaerens. Because of a lack of relevant information on the safety of this bacterium, including the genetic basis of antibiotic resistance in the production strain, it has not been recommended for use in the "qualified presumption of safety" (QPS) list and subsequent updated lists. The current study shows no safety issue of E. adhaerens YX1 in terms of its antibiotic resistance. These results are important as they provide an initial basis for an understanding of the antibiotic resistance/susceptibility of E. adhaerens YX1 (CICC 11008s), which produces vitamin B12 and is widely used in the food and feed industry.

Bacterial Antibiotic Resistance: on the Cusp of a Post-antibiotic World

The specific aim of this article is to provide evidence that antibiotic resistance (AR) has become a human disease unto itself and to describe the current means of preventing, treating, and reversing AR in individuals and in affected populations. An ever-increasing number of infections are being classified as multidrug resistant (MDR). Low and middle-income countries are most likely to increase the spread of AR due to limited healthcare infrastructure coupled with policies that promote unregulated access to antibiotics. The genetic basis for AR has become more thoroughly understood as efforts move toward a global big data approach to surveille and implement effective public health measures. Antibiotic Stewardship (AS) programs are critical to prevent the spread of AR. As resistant pathogens reside in patients for many years after they are initially integrated into the microbiome, the potential for future infection increases substantially. This property contributes to the conclusion that AR is in and of itself a human disease that must be treated appropriately. While all bacteria are at risk to become AR, Staphylococcus, Klebsiella, Mycobacterium, Acinetobacter, and Pseudomonas represent the greatest challenges in infectious disease treatment as rapid AR acquisition leads to MDR infections.

79-Year-Old Man With Shortness of Breath and Fevers

79-Year-Old Man With Shortness of Breath and Fevers

Novel Tn916-like elements confer aminoglycoside/macrolide co-resistance in clinical isolates of Streptococcus gallolyticus ssp. gallolyticus.

Streptococcus gallolyticus ssp. gallolyticus (Sgg) is a commensal bacterium and an opportunistic pathogen. In humans it has been clinically associated with the incidence of colorectal cancer (CRC) and epidemiologically recognized as an emerging cause of infective endocarditis (IE). The standard therapy of Sgg includes the administration of a penicillin in combination with an aminoglycoside. Even though penicillin-resistant isolates have still not been reported, epidemiological studies have shown that this microbe is a reservoir of multiple acquired genes, conferring resistance to tetracyclines, aminoglycosides, macrolides and glycopeptides. However, the underlying antibiotic resistance mobilome of Sgg remains poorly understood. To investigate the mobile genetic basis of antibiotic resistance in multiresistant clinical Sgg. Isolate NTS31106099 was recovered from a patient with IE and CRC at Nantes University Hospital, France and studied by Illumina WGS and comparative genomics. Molecular epidemiology of the identified mobile element(s) was performed using antibiotic susceptibility testing (AST), PCR, PFGE and WGS. Mobility was investigated by PCR and filter mating. Two novel conjugative transposons, Tn6263 and Tn6331, confer aminoglycoside/macrolide co-resistance in clinical Sgg. They display classical family Tn916/Tn1545 modular architecture and harbour an aph(3')-III→sat4→ant(6)-Ia→erm(B) multiresistance gene cluster, related to pRE25 of Enterococcus faecium. These and/or closely related elements are highly prevalent among genetically heterogeneous clinical isolates of Sgg. Previously unknown Tn916-like mobile genetic elements conferring aminoglycoside/macrolide co-resistance make Sgg, collectively with other gut Firmicutes such as enterococci and eubacteria, a potential laterally active reservoir of these antibiotic resistance determinants among the mammalian gastrointestinal microbiota.

Nanoemulsion is an effective antimicrobial for methicillin-resistant Staphylococcus aureus in infected wounds.

To develop NB-201, a nanoemulsion compound, as a novel microbicidal agent against methicillin-resistant Staphylococcus aureus (MRSA) infection, which is a common threat to public health but with limited therapeutic options. NB-201 was tested in in vitro and in vivo murine and porcine models infected with MRSA. Topical treatment of MRSA-infected wounds with NB-201 significantly decreased bacterial load and had no toxic effects on healthy skin tissues. NB-201 attenuated neutrophil sequestration in MRSA-infected wounds and inhibited epidermal and deep dermal inflammation. The levels of proinflammatory cytokines were reduced in NB-201-treated MRSA-infected wounds. NB-201 can greatly reduce inflammation characteristic of infected wounds and has antimicrobial activity that effectively kills MRSA regardless of the genetic basis of antibiotic resistance.

Resistance to antimicrobial drugs in different surface waters and wastewaters of Guadeloupe.

ObjectiveThe first aim of this study was to evaluate the antimicrobial resistance of Enterobacteriaceae in different water environments of Guadeloupe and especially those impacted by waste water treatment plants (WWTP) effluents.The second objective was to characterize the genetic basis for antibiotic resistance of extended-spectrum beta-lactamase (ESBL) and AmpC beta-lactamase producing Enterobacteriaceae isolates (ESBLE and AmpCE).MethodsWe have collected 70 surface waters (river and sea samples) impacted or not by WWTP and 18 waste waters from 2 WWTPs in 2012 and 2013. We i) determined the total and resistant bacterial counts and ii) tested isolated Enterobacteriaceae for their antimicrobial susceptibility. We also studied the genetic basis for antibiotic resistance of ESBLE and AmpCE, and the genetic background of Escherichia coli.ResultsIn rivers, contamination with Escherichia coli and antibiotic resistant coliforms (ARC) increased from the source to the mouth. Highest levels of river contamination with E. coli (9.26 x 105 MPN/100mL) and ARC (2.26 x 108 CFU/mL) were observed in surface water sampled near the discharge. A total of 246 Enterobacteriaceae strains resistant to antibiotics were isolated, mostly from waste waters and from river water collected near the discharge. Among these strains, 33 were Extended Spectrum Beta Lactamase (ESBLE) and 8 E. coli were AmpC beta-lactamase producers. All the ESBLE were isolated from waste waters or from river water collected near the discharge. The blaCTX-M gene was present in 29 of the 33 ESBLE strains, with 24 belonging to group 1. Numerous strains (68.7%) showed more than one acquired antibiotic resistance mechanism. E. coli strains belonged to different phylogenetic groups; among the B2 group, most strains belonged to the ST131 clone.ConclusionOur results demonstrated that many human activities can supply antibiotic-resistant bacteria in surface water. Nevertheless, WWTPs were the most important supplier of ESBLE in water environment of Guadeloupe.

High third-generation cephalosporin resistant Enterobacteriaceae prevalence rate among neonatal infections in Dakar, Senegal.

BackgroundNeonatal infection constitutes one of Senegal’s most important public health problems, with a mortality rate of 41 deaths per 1,000 live births.MethodsBetween January 2007 and March 2008, 242 neonates with suspected infection were recruited at three neonatal intensive care units in three major tertiary care centers in Dakar, the capital of Senegal. Neonatal infections were confirmed by positive bacterial blood or cerebrospinal fluid culture. The microbiological pattern of neonatal infections and the antibiotic susceptibility of the isolates were characterized. In addition, the genetic basis for antibiotic resistance and the genetic background of third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae were studied.ResultsA bacteriological infection was confirmed in 36.4 % (88/242) of neonates: 22.7 % (30/132) during the early-onset and 52.7 % (58/110) during the late-onset periods (p > 0.20). Group B streptococci accounted for 6.8 % of the 88 collected bacterial isolates, while most of them were Enterobacteriaceae (n = 69, 78.4 %). Of these, 55/69 (79.7 %) were 3GC-R. The bla CTX-M-15 allele, the bla SHV and the bla TEM were highly prevalent (63.5, 65.4 and 53.8 %, respectively), usually associated with qnr genes (65.4 %). Clonally related strains of 3GC-R Klebsiella pneumoniae and 3GC-R Enterobacter cloacae, the two most commonly recovered 3GC-R Enterobacteriaceae (48/55), were detected at the three hospitals, underlining the role of cross-transmission in their spread. The overall case fatality rate was 18.6 %.ConclusionsMeasures should be taken to prevent nosocomial infections and the selection of resistant bacteria.

High rate of faecal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae in healthy children in Bangui, Central African Republic

The aim of this study was to estimate the prevalence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) in faeces of healthy children aged 0–59 months in Bangui (Central African Republic). Stool samples of 134 children, recruited for a matched case-control study, were cultured on a commercial ESBL-selective chromogenic medium (CHROMagar ESBL, France). The phenotypic resistance patterns of isolated strains were investigated, as well as the genetic basis for antibiotic resistance. The factors associated with increased risk for ESBL-E carriage were also studied. The prevalence of ESBL-E carriage was 59% (79/134), one of the highest reported worldwide. The only factor found to be associated with carriage was living in a highest-income family (p=0.03). In all, 83 ESBL-E were recovered as simultaneous carriage of two strains was detected in four children. blaCTX-M-15 was found in all strains except two, frequently associated with qnr (54/81, 66%) and aac(6′)-Ib-cr (35/81, 43%) genes. Escherichia coli, the most commonly recovered species (51/83, 61%), was assigned mainly to the pandemic B2-O25b-ST131 group (39/51, 76%). Resistance transfer, which was studied in 20 randomly selected ESBL-E strains, was successful in 13 (13/20, 65%) isolates. In eight of these isolates (8/13, 62%), blaCTX-M-15 genes were found in incompatibility group FIb conjugative plasmids. We found one of the highest prevalence rates of faecal carriage of ESBL-E reported worldwide, highlighting the need to improve control of the distribution of antibiotics in limited-resource countries.

Dissemination of IncF-type plasmids in multiresistant CTX-M-15-producing Enterobacteriaceae isolates from surgical-site infections in Bangui, Central African Republic

BackgroundSurgical-site infection is the most frequent health care-associated infection in the developing world, with a strikingly higher prevalence than in developed countries We studied the prevalence of resistance to antibiotics in Enterobacteriaceae isolates from surgical-site infections collected in three major tertiary care centres in Bangui, Central African Republic. We also studied the genetic basis for antibiotic resistance and the genetic background of third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae.ResultsBetween April 2011 and April 2012, 195 patients with nosocomial surgical-site infections were consecutively recruited into the study at five surgical departments in three major tertiary care centres. Of the 165 bacterial isolates collected, most were Enterobacteriaceae (102/165, 61.8%). Of these, 65/102 (63.7%) were 3GC-R, which were characterized for resistance gene determinants and genetic background. The blaCTX-M-15 and aac(6′)-Ib-cr genes were detected in all strains, usually associated with qnr genes (98.5%). Escherichia coli, the most commonly recovered species (33/65, 50.8%), occurred in six different sequence types, including the pandemic B2-O25b-ST131 group (12/33, 36.4%). Resistance transfer was studied in one representative strain of the resistance gene content in each repetitive extragenic palindromic and enterobacterial repetitive intergenic consensus sequence-PCR banding pattern. Plasmids were characterized by PCR-based replicon typing and sub-typing schemes. In most isolates (18/27, 66.7%), blaCTX-M-15 genes were found in incompatibility groups F/F31:A4:B1 and F/F36:A4:B1 conjugative plasmids. Horizontal transfer of both plasmids is probably an important mechanism for the spread of blaCTX-M-15 among Enterobacteriaceae species and hospitals. The presence of sets of antibiotic resistance genes in these two plasmids indicates their capacity for gene rearrangement and their evolution into new variants.ConclusionsDiverse modes are involved in transmission of resistance, plasmid dissemination probably playing a major role.

Linking system-wide impacts of RNA polymerase mutations to the fitness cost of rifampin resistance in Pseudomonas aeruginosa.

ABSTRACTFitness costs play a key role in the evolutionary dynamics of antibiotic resistance in bacteria by generating selection against resistance in the absence of antibiotics. Although the genetic basis of antibiotic resistance is well understood, the precise molecular mechanisms linking the genetic basis of resistance to its fitness cost remain poorly characterized. Here, we examine how the system-wide impacts of mutations in the RNA polymerase (RNAP) gene rpoB shape the fitness cost of rifampin resistance in Pseudomonas aeruginosa. Rifampin resistance mutations reduce transcriptional efficiency, and this explains 76% of the variation in fitness among rpoB mutants. The pleiotropic consequence of rpoB mutations is that mutants show altered relative transcript levels of essential genes. We find no evidence that global transcriptional responses have an impact on the fitness cost of rifampin resistance as revealed by transcriptome sequencing (RNA-Seq). Global changes in the transcriptional profiles of rpoB mutants compared to the transcriptional profile of the rifampin-sensitive ancestral strain are subtle, demonstrating that the transcriptional regulatory network of P. aeruginosa is robust to the decreased transcriptional efficiency associated with rpoB mutations. On a smaller scale, we find that rifampin resistance mutations increase the expression of RNAP due to decreased termination at an attenuator upstream from rpoB, and we argue that this helps to minimize the cost of rifampin resistance by buffering against reduced RNAP activity. In summary, our study shows that it is possible to dissect the molecular mechanisms underpinning variation in the cost of rifampin resistance and highlights the importance of genome-wide buffering of relative transcript levels in providing robustness against resistance mutations.

Antibiotic resistance of bacteria: A global challenge

Bacterial resistance to antibiotics poses a serious challenge to the prospect of chemotherapy. Rational use of antibiotics is most desirable but it cannot provide a permanent solution to the problem. In this article the biochemical and genetic basis of antibiotic resistance in bacteria is discussed with examples. The non-clinical aspects of antibiotic-resistance are also dealt with in brief.

Genetic basis of antibiotic resistance in pathogenic Acinetobacter species

Antibiotic resistance in Acinetobacter spp., particularly Acinetobacter baumannii, is increasing rapidly. A. baumannii possesses two intrinsic β-lactamase genes, in addition to weak permeability and efflux systems, that together confer a natural reduced susceptibility to antibiotics. In addition, numerous acquired mechanisms of resistance have been identified in A. baumannii. The very high genetic plasticity of A. baumannii allows an accumulation of resistance determinants that give rise to multidrug resistance at an alarming rate. The role of novel genetic elements, such as resistance islands, in concentrating antibiotic resistance genes in A. baumannii requires detailed investigation in the near future.

Stenotrophomonas maltophilia: emerging disease patterns and challenges for treatment

Stenotrophomonas maltophilia is a ubiquitous organism associated with opportunistic infections. In the immunocompromised host, increasing prevalence and severity of illness is observed, particularly opportunistic bloodstream infections and pneumonia syndromes. In this article, the classification and microbiology are outlined, together with clinical presentation, outcomes and management of infections due to S. maltophilia. Although virulence mechanisms and the genetic basis of antibiotic resistance have been identified, a role for standardized and uniform reporting of antibiotic sensitivity is not defined. Infections due to S. maltophilia have traditionally been treated with trimethoprim–sulfamethoxazole, ticarcillin–clavulanic acid, or fluoroquinolone agents. The use of combination therapies, newer fluoroquinolone agents and tetracycline derivatives is discussed. Finally, measures to prevent transmission of S. maltophilia within healthcare facilities are reported, especially in at-risk patient populations.