# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 6247 | 0 | 1.0000 | Molecular basis and evolutionary cost of a novel macrolides/lincosamides resistance phenotype in Staphylococcus haemolyticus. Staphylococcus haemolyticus (S. haemolyticus) is a coagulase-negative Staphylococcus that has become one of the primary causes of nosocomial infection. After a long period of antibiotic use, S. haemolyticus has developed multiple resistance phenotypes for macrolides and lincosamides. Herein, we evaluated four S. haemolyticus clinical isolates, of which three had antibiotic resistance patterns reported previously. The fourth isolate was resistant to both erythromycin and clindamycin in the absence of erythromycin induction. This novel phenotype, known as constitutive macrolides-lincosamides-streptogramins resistance, has been reported in other bacteria but has not been previously reported in S. haemolyticus. Investigation of the isolate demonstrated a deletion in the methyltransferase gene ermC, upstream leader peptide. This deletion resulted in constitutive MLS resistance based on whole-genome sequencing and experimental verification. Continuous expression of ermC was shown to inhibit the growth of S. haemolyticus, which turned out to be the fitness cost with no MLS pressure. In summary, this study is the first to report constitutive MLS resistance in S. haemolyticus, which provides a better understanding of MLS resistance in clinical medicine. IMPORTANCE This study identified a novel phenotype of macrolides/lincosamides resistance in Staphylococcus haemolyticus which improved a better guidance for clinical treatment. It also clarified the mechanistic basis for this form of antibiotic resistance that supplemented the drug resistance mechanism of Staphylococcus. In addition, this study elaborated on a possibility that continuous expression of some resistance genes was shown to inhibit the growth of bacteria themselves, which turned out to be the fitness cost in the absence of antibiotic pressure. | 2023 | 37724875 |
| 6248 | 1 | 0.9999 | Characterization of a stable, metronidazole-resistant Clostridium difficile clinical isolate. BACKGROUND: Clostridium difficile are gram-positive, spore forming anaerobic bacteria that are the leading cause of healthcare-associated diarrhea, usually associated with antibiotic usage. Metronidazole is currently the first-line treatment for mild to moderate C. difficile diarrhea however recurrence occurs at rates of 15-35%. There are few reports of C. difficile metronidazole resistance in the literature, and when observed, the phenotype has been transient and lost after storage or exposure of the bacteria to freeze/thaw cycles. Owing to the unstable nature of the resistance phenotype in the laboratory, clinical significance and understanding of the resistance mechanisms is lacking. METHODOLOGY/PRINCIPAL FINDINGS: Genotypic and phenotypic characterization was performed on a metronidazole resistant clinical isolate of C. difficile. Whole-genome sequencing was used to identify potential genetic contributions to the phenotypic variation observed with molecular and bacteriological techniques. Phenotypic observations of the metronidazole resistant strain revealed aberrant growth in broth and elongated cell morphology relative to a metronidazole-susceptible, wild type NAP1 strain. Comparative genomic analysis revealed single nucleotide polymorphism (SNP) level variation within genes affecting core metabolic pathways such as electron transport, iron utilization and energy production. CONCLUSIONS/SIGNIFICANCE: This is the first characterization of stable, metronidazole resistance in a C. difficile isolate. The study provides an in-depth genomic and phenotypic analysis of this strain and provides a foundation for future studies to elucidate mechanisms conferring metronidazole resistance in C. difficile that have not been previously described. | 2013 | 23349739 |
| 4484 | 2 | 0.9998 | A Review of the Impact of Streptococcal Infections and Antimicrobial Resistance on Human Health. Streptococcus pneumoniae, Streptococcus pyogenes (GAS), and Streptococcus agalactiae (GBS) are bacteria that can cause a range of infections, some of them life-threatening. This review examines the spread of antibiotic resistance and its mechanisms against antibiotics for streptococcal infections. Data on high-level penicillin-resistant invasive pneumococci have been found in Brazil (42.8%) and Japan (77%). The resistance is caused by mutations in genes that encode penicillin-binding proteins. Similarly, GAS and GBS strains reported from Asia, the USA, and Africa have undergone similar transformations in PBPs. Resistance to major alternatives of penicillins, macrolides, and lincosamides has become widespread among pneumococci and streptococci, especially in Asia (70-95%). The combination of several emm types with erm(B) is associated with the development of high-level macrolide resistance in GAS. Major mechanisms are ribosomal target modifications encoded by erm genes, ribosomal alterations, and active efflux pumps that regulate antibiotic entry due to mefA/E and msrD genes. Tetracycline resistance for streptococci in different countries varied from 22.4% in the USA to 83.7/100% in China, due to tet genes. Combined tetracycline/macrolide resistance is usually linked with the insertion of ermB into the transposon carrying tetM. New quinolone resistance is increasing by between 11.5 and 47.9% in Asia and Europe. The mechanism of quinolone resistance is based on mutations in gyrA/B, determinants for DNA gyrase, or parC/E encoding topoisomerase IV. The results for antibiotic resistance are alarming, and urgently call for increased monitoring of this problem and precautionary measures for control to prevent the spread of resistant mutant strains. | 2024 | 38667036 |
| 6266 | 3 | 0.9998 | Bacterial gene loss as a mechanism for gain of antimicrobial resistance. Acquisition of exogenous DNA by pathogenic bacteria represents the basis for much of the acquired antimicrobial resistance in pathogenic bacteria. A more extreme mechanism to avoid the effect of an antibiotic is to delete the drug target, although this would be predicted to be rare since drug targets are often essential genes. Here, we review and discuss the description of a novel mechanism of resistance to the cephalosporin drug ceftazidime caused by loss of a penicillin-binding protein (PBP) in a Gram-negative bacillus (Burkholderia pseudomallei). This organism causes melioidosis across south-east Asia and northern Australia, and is usually treated with two or more weeks of ceftazidime followed by oral antibiotics for three to six months. Comparison of clinical isolates from six patients with melioidosis found initial ceftazidime-susceptible isolates and subsequent ceftazidime-resistant variants. The latter failed to grow on commonly used culture media, rendering these isolates difficult to detect in the diagnostic laboratory. Genomic analysis using pulsed-field gel electrophoresis and array based genomic hybridisation revealed a large-scale genomic deletion comprising 49 genes in the ceftazidime-resistant strains. Mutational analysis of wild-type B. pseudomallei demonstrated that ceftazidime resistance was due to deletion of a gene encoding a PBP 3 present within the region of genomic loss. This provides one explanation for ceftazidime treatment failure, and may be a frequent but undetected event in patients with melioidosis. | 2012 | 23022568 |
| 4414 | 4 | 0.9998 | Macrolide resistance mechanisms in Gram-positive cocci. Two principal mechanisms of resistance to macrolides have been identified in Gram-positive bacteria. Erythromycin-resistant methylase is encoded by erm genes. Resultant structural changes to rRNA prevent macrolide binding and allow synthesis of bacterial proteins to continue. Presence of the erm gene results in high-level resistance. Modification of the mechanism whereby antibiotics are eliminated from the bacteria also brings about resistance. Bacteria carrying the gene encoding macrolide efflux (i.e. the mefE gene) display relatively low-level resistance. Azithromycin, because of its ability to achieve concentrations at sites of infections, is capable of eradicating mefE-carrying strains. Other resistance mechanisms, involving stimulation of enzymatic degradation, appear not to be clinically significant. | 2001 | 11574191 |
| 4483 | 5 | 0.9998 | Ribosomal Resistance: Emerging Problems and Potential Solutions. Many systemic antibiotics use ribosomal inhibition to suppress the replication of bacteria. Current research suggests that resistance to macrolide, lincosamide, and streptogramin B (MLS(B)) antibiotics is emerging among clinical isolates of Streptococcus pyogenes and Streptococcus pneumoniae. Erythromycin methylases, encoded by erm genes, modify an essential adenine residue in 23S rRNA and confer cross-resistance to MLS(B) antibiotics. More recently, macrolide efflux (mef) genes were identified in isolates of S. pyogenes and S. pneumoniae that show resistance to 14- and 15-membered macrolides (M phenotype). Resistance to MLSB has been associated with the increased use of erythromycin, and the recent emergence of the M phenotype has coincided with the marketing of newer macrolides. However, despite increasing macrolide resistance among clinical isolates of S. pneumoniae, convincing data on treatment failures directly attributable to MLS(B) or M phenotypes are limited. Possible solutions to emerging MLS(B) and M phenotype resistance include the introduction of alternative antibiotics, the more prudent use of antibiotics, combination therapy, molecular diagnostics, enhanced understanding of pharmacodynamic variables, and redefined resistance breakpoints. | 1999 | 11095824 |
| 4497 | 6 | 0.9998 | Detection and expression analysis of tet(B) in Streptococcus oralis. Tetracycline resistance can be achieved through tet genes, which code for efflux pumps, ribosomal protection proteins and inactivation enzymes. Some of these genes have only been described in either Gram-positive or Gram-negative bacteria. This is the case of tet(B), which codes for an efflux pump and, so far, had only been found in Gram-negative bacteria. In this study, tet(B) was detected in two clinical Streptococcus oralis strains isolated from the gingival sulci of two subjects. In both cases, the gene was completely sequenced, yielding 100% shared identity and coverage with other previously published sequences of tet(B). Moreover, we studied the expression of tet(B) using RT-qPCR in the isolates grown with and without tetracycline, detecting constitutive expression in only one of the isolates, with no signs of expression in the other one. This is the first time that the presence and expression of the tet(B) gene has been confirmed in Gram-positive bacteria, which highlights the potential of the genus Streptococcus to become a reservoir and a disseminator of antibiotic resistance genes in an environment so prone to horizontal gene transfer as is the oral biofilm. | 2019 | 31448060 |
| 4798 | 7 | 0.9998 | Acquired vancomycin resistance in clinically relevant pathogens. Acquired resistance to vancomycin is an increasing problem in pathogenic bacteria. It is best studied and most prevalent among Enterococcus and still remains rare in other pathogenic bacteria. Different genotypes of vancomycin resistance, vanA-G, have been described. The different van gene clusters consist of up to nine genes encoding proteins of different functions; their interplay leads to an alternative cell wall precursor less susceptible to glycopeptide binding. Variants of vanA and vanB types are found worldwide, with vanA predominating; their reservoir is Enterococcus faecium. Within this species a subpopulation of hospital-adapted types exists that acquired van gene clusters and which is responsible for outbreaks of vancomycin-resistant enterococci all over the world. Acquisition of vanA by methicillin-resistant Staphylococcus aureus (MRSA) is worrisome and seven cases have been described. Nonsusceptibility to glycopeptides also occurs independently from van genes and is a growing therapeutic challenge, especially in MRSA. | 2008 | 18811239 |
| 4677 | 8 | 0.9998 | Antibiotic susceptibility of plant-derived lactic acid bacteria conferring health benefits to human. Lactic acid bacteria (LAB) confer health benefits to human when administered orally. We have recently isolated several species of LAB strains from plant sources, such as fruits, vegetables, flowers, and medicinal plants. Since antibiotics used to treat bacterial infection diseases induce the emergence of drug-resistant bacteria in intestinal microflora, it is important to evaluate the susceptibility of LAB strains to antibiotics to ensure the safety and security of processed foods. The aim of the present study is to determine the minimum inhibitory concentration (MIC) of antibiotics against several plant-derived LAB strains. When aminoglycoside antibiotics, such as streptomycin (SM), kanamycin (KM), and gentamicin (GM), were evaluated using LAB susceptibility test medium (LSM), the MIC was higher than when using Mueller-Hinton (MH) medium. Etest, which is an antibiotic susceptibility assay method consisting of a predefined gradient of antibiotic concentrations on a plastic strip, is used to determine the MIC of antibiotics world-wide. In the present study, we demonstrated that Etest was particularly valuable while testing LAB strains. We also show that the low susceptibility of the plant-derived LAB strains against each antibiotic tested is due to intrinsic resistance and not acquired resistance. This finding is based on the whole-genome sequence information reflecting the horizontal spread of the drug-resistance genes in the LAB strains. | 2019 | 31399643 |
| 4595 | 9 | 0.9998 | Transfer of mupirocin resistance from Staphylococcus haemolyticus clinical strains to Staphylococcus aureus through conjugative and mobilizable plasmids. Coagulase-negative staphylococci are thought to act as reservoirs of antibiotic resistance genes that can be transferred to Staphylococcus aureus, thus hindering the combat of this bacterium. In this work, we analyzed the presence of plasmids conferring resistance to the antibiotic mupirocin-widely used to treat and prevent S. aureus infections in hospital environments-in nosocomial S. haemolyticus strains. About 12% of the 75 strains tested were resistant to mupirocin, and this phenotype was correlated with the presence of plasmids. These plasmids were shown to be diverse, being either conjugative or mobilizable, and capable of transferring mupirocin resistance to S. aureus Our findings reinforce that S. haemolyticus, historically and mistakenly considered as a less important pathogen, is a reservoir of resistance genes which can be transferred to other bacteria, such as S. aureus, emphasizing the necessity of more effective strategies to detect and combat this emergent opportunistic pathogen. | 2016 | 27190144 |
| 4930 | 10 | 0.9998 | Whole-genome sequencing based characterization of antimicrobial resistance in Enterococcus. Whole-genome sequencing (WGS) has transformed our understanding of antimicrobial resistance, yielding new insights into the genetics underlying resistance. To date, most studies using WGS to study antimicrobial resistance have focused on gram-negative bacteria in the family Enterobacteriaceae, such as Salmonella spp. and Escherichia coli, which have well-defined resistance mechanisms. In contrast, relatively few studies have been performed on gram-positive organisms. We sequenced 197 strains of Enterococcus from various animal and food sources, including 100 Enterococcus faecium and 97 E. faecalis. From analyzing acquired resistance genes and known resistance-associated mutations, we found that resistance genotypes correlated with resistance phenotypes in 96.5% of cases for the 11 drugs investigated. Some resistances, such as those to tigecycline and daptomycin, could not be investigated due to a lack of knowledge of mechanisms underlying these phenotypes. This study showed the utility of WGS for predicting antimicrobial resistance based on genotype alone. | 2018 | 29617860 |
| 5977 | 11 | 0.9998 | Methods to determine antibiotic resistance gene silencing. The occurrence of antibiotic-resistant bacteria is an increasingly serious problem world-wide. In addition, to phenotypically resistant bacteria, a threat may also be posed by isolates with silent, but intact, antibiotic resistance genes. Such isolates, which have recently been described, possess wild-type genes that are not expressed, but may convert to resistance by activating expression of the silent genes. They may therefore compromise the efficacy of antimicrobial treatment, particularly if their presence has not been diagnosed. This chapter describes the detection of silent resistance genes by PCR and DNA sequencing. A method to detect five potentially silent acquired resistance genes; aadA, bla (OXA-2), strAB, sul1, and tet(A) is described. First, the susceptibility of the isolates to the relevant antibiotics is determined by an appropriate susceptibility testing method, such as E-test. Then the presence of the genes is investigated by PCR followed by agarose gel electrophoresis of the amplification products. If a resistance gene is detected in a susceptible isolate, the entire open-reading frame and promoter sequence of the gene is amplified by PCR and their DNA sequences obtained. The DNA sequences are then compared to those of known resistant isolates, to detect mutations that may account for susceptibility. If no mutations are detected the expression of the gene is investigated by RT-PCR following RNA extraction. The methods described here can be applied to all acquired resistance genes for which sequence and normal expression data are available. | 2010 | 20401584 |
| 4487 | 12 | 0.9998 | Detecting mutations that confer oxazolidinone resistance in gram-positive bacteria. Resistance to oxazolidinone antibiotics, including linezolid, in Gram-positive bacteria is mediated by single-nucleotide polymorphisms (SNPs) in the 23S ribosomal RNA. A G2576U change (encoded by a G2576T mutation in the rRNA genes) is found in most resistant clinical isolates of enterococci and staphylococci; a variety of changes have been found in resistant mutants selected in vitro. Pyrosequencing can be used to detect SNPs known to confer oxazolidinone resistance, including the G2576T change. Most bacteria have more than one rRNA gene copy and Pyrosequencing can also be used for allele quantification, i.e., to estimate the proportions of mutant vs wild-type alleles. The number of mutated rRNA gene copies correlates roughly with the level of oxazolidinone resistance displayed by resistant isolates. This chapter summarizes the Pyrosequencing assays that have been developed in our laboratory for analyzing oxazolidinone-resistant enterococci and staphylococci. | 2007 | 17185761 |
| 6246 | 13 | 0.9998 | The CRISPR System and MepA Multidrug Efflux Pump Linked to Antibiotic Resistance in Staphylococcus aureus. Staphylococcus aureus (S. aureus) is a major zoonotic pathogen. To investigate CRISPR carriage in S. aureus isolates from cows with mastitis and the role of the CRISPR system and efflux pumps in antibiotic resistance. We analyzed antibiotic resistance genes and CRISPR loci, sequenced spacers, and assessed correlations between CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) presence and antibiotic resistance in 234 S. aureus isolates. The changes in CRISPR sequences were examined by continuous passage of 360 generations without antibiotic pressure. Subsequently, variations in CRISPR loci and transcript levels were measured under ciprofloxacin (CIP) exposure. In addition, an S. aureus-25-mepA was constructed to evaluate changes in antimicrobial sensitivity and mepA transcript levels in both planktonic and biofilm states. Our results revealed a CRISPR loci detection rate of 7.69% among the 234 S. aureus isolates, with significantly lower rates of the antibiotic resistance genes gyrA, grlA, norA, and tet(M) in CRISPR-positive isolates compared to those in CRISPR-negative isolates (p < 0.05). CIP-resistant strains exhibited loss of repeat and spacer sequence in CRISPR loci, and the transcript abundance of these loci gradually decreased under CIP pressures, indicating that CRISPR loci deletion or transcript level downregulation under antibiotic stress may be a potential regulatory mechanism of antibiotic resistance. Correlation analysis linked CIP resistance in both planktonic and biofilm S. aureus to mepA transcript levels and biofilm integrity. Our study provides insight into the mechanism by which S. aureus develops antibiotic resistance via the CRISPR system and the MepA efflux pump, offering a theoretical foundation for monitoring the prevalence and resistance of pathogenic bacteria. | 2025 | 39977007 |
| 4641 | 14 | 0.9998 | Genomic insights into antibiotic resistance and mobilome of lactic acid bacteria and bifidobacteria. Lactic acid bacteria (LAB) and Bifidobacterium sp. (bifidobacteria) can carry antimicrobial resistance genes (ARGs), yet data on resistance mechanisms in these bacteria are limited. The aim of our study was to identify the underlying genetic mechanisms of phenotypic resistance in 103 LAB and bifidobacteria using whole-genome sequencing. Sequencing data not only confirmed the presence of 36 acquired ARGs in genomes of 18 strains, but also revealed wide dissemination of intrinsic ARGs. The presence of acquired ARGs on known and novel mobile genetic elements raises the possibility of their horizontal spread. In addition, our data suggest that mutations may be a common mechanism of resistance. Several novel candidate resistance mechanisms were uncovered, providing a basis for further in vitro studies. Overall, 1,314 minimum inhibitory concentrations matched with genotypes in 92.4% of the cases; however, prediction of phenotype based on genotypic data was only partially efficient, especially with respect to aminoglycosides and chloramphenicol. Our study sheds light on resistance mechanisms and their transferability potential in LAB and bifidobacteria, which will be useful for risk assessment analysis. | 2023 | 36781180 |
| 6249 | 15 | 0.9998 | Genome-Wide Identification of Antimicrobial Intrinsic Resistance Determinants in Staphylococcus aureus. The emergence of antimicrobial resistance severely threatens our ability to treat bacterial infections. While acquired resistance has received considerable attention, relatively little is known of intrinsic resistance that allows bacteria to naturally withstand antimicrobials. Gene products that confer intrinsic resistance to antimicrobial agents may be explored for alternative antimicrobial therapies, by potentiating the efficacy of existing antimicrobials. In this study, we identified the intrinsic resistome to a broad spectrum of antimicrobials in the human pathogen, Staphylococcus aureus. We screened the Nebraska Transposon Mutant Library of 1920 single-gene inactivations in S. aureus strain JE2, for increased susceptibility to the anti-staphylococcal antimicrobials (ciprofloxacin, oxacillin, linezolid, fosfomycin, daptomycin, mupirocin, vancomycin, and gentamicin). Sixty-eight mutants were confirmed by E-test to display at least twofold increased susceptibility to one or more antimicrobial agents. The majority of the identified genes have not previously been associated with antimicrobial susceptibility in S. aureus. For example, inactivation of genes encoding for subunits of the ATP synthase, atpA, atpB, atpG and atpH, reduced the minimum inhibitory concentration (MIC) of gentamicin 16-fold. To elucidate the potential of the screen, we examined treatment efficacy in the Galleria mellonella infection model. Gentamicin efficacy was significantly improved, when treating larvae infected with the atpA mutant compared to wild type cells with gentamicin at a clinically relevant concentration. Our results demonstrate that many gene products contribute to the intrinsic antimicrobial resistance of S. aureus. Knowledge of these intrinsic resistance determinants provides alternative targets for compounds that may potentiate the efficacy of existing antimicrobial agents against this important pathogen. | 2016 | 28066345 |
| 4380 | 16 | 0.9998 | Comparative genome analysis of ciprofloxacin-resistant Pseudomonas aeruginosa reveals genes within newly identified high variability regions associated with drug resistance development. The alarming rise of ciprofloxacin-resistant Pseudomonas aeruginosa has been reported in several clinical studies. Though the mutation of resistance genes and their role in drug resistance has been researched, the process by which the bacterium acquires high-level resistance is still not well understood. How does the genomic evolution of P. aeruginosa affect resistance development? Could the exposure of antibiotics to the bacteria enrich genomic variants that lead to the development of resistance, and if so, how are these variants distributed through the genome? To answer these questions, we performed 454 pyrosequencing and a whole genome analysis both before and after exposure to ciprofloxacin. The comparative sequence data revealed 93 unique resistance strain variation sites, which included a mutation in the DNA gyrase subunit A gene. We generated variation-distribution maps comparing the wild and resistant types, and isolated 19 candidates from three discrete resistance-associated high variability regions that had available transposon mutants, to perform a ciprofloxacin exposure assay. Of these region candidates with transposon disruptions, 79% (15/19) showed a reduction in the ability to gain high-level resistance, suggesting that genes within these high variability regions might enrich for certain functions associated with resistance development. | 2013 | 23808957 |
| 4393 | 17 | 0.9998 | Mechanisms of Staphylococcus aureus Antibiotics Resistance Revealed by Adaptive Laboratory Evolution. Infection caused by drug-resistant Staphylococcus aureus is a serious public health and veterinary concern. Lack of a comprehensive understanding of the mechanisms underlying the emergence of drug-resistant strains, it makes S. aureus one of the most intractable pathogenic bacteria. To identify mutations that confer resistance to anti-S. aureus drugs, we established a laboratory-based adaptive evolution system and performed 10 rounds of evolution experiments against 15 clinically used antibiotics. We discovered a panel of known and novel resistance-associated sites after performing whole-genome sequencing. Furthermore, we found that the resistance evolved at distinct rates. For example, streptomycin, rifampicin, fusidic acid and novobiocin all developed significant resistance quickly in the second round of evolution. Intriguingly, the cross-resistance experiment reveals that nearly all drug-resistant strains have varying degrees of increased sensitivity to fusidic acid, pointing to a novel approach to battle AMR. In addition, the in silico docking analysis shows that the evolved mutants affect the interaction of rifampcin-rpoB, as well as the novobiocin-gyrB. Moreover, for the genes we got in the laboratory evolution, mutant genes of clinical isolates of human had significant differences from the environmental isolates and animal isolates. We believe that the strategy and data set in this research will be helpful for battling AMR issue of S. aureus, and adaptable to other pathogenic microbes. | 2025 | 39762552 |
| 4754 | 18 | 0.9998 | Enterococci and streptococci. Besides Staphylococcus aureus, other Gram-positive bacteria have become multidrug-resistant and cause therapeutic problems, particularly amongst hospitalised patients. The acquisition of vancomycin resistance by strains of Enterococcus faecium and Enterococcus faecalis is of particular concern and has resulted in treatment failures. Some of the infections caused by these bacteria do respond to treatment with new antibiotics that have been released in the last few years, however more options are required as not all enterococci are inherently susceptible and resistance is beginning to emerge amongst those that were susceptible. Resistance to commonly used antibiotics is also emerging in Streptococcus spp., particularly to the tetracyclines and macrolides. In both genera, multiresistant strains spread between patients and between hospitals. In the laboratory, these bacteria show considerable susceptibility to tigecycline, with little propensity to develop resistance, indicating that tigecycline could assume an important role in controlling infections caused by these Gram-positive bacteria. | 2007 | 17659211 |
| 4635 | 19 | 0.9998 | A Gene Homologous to rRNA Methylase Genes Confers Erythromycin and Clindamycin Resistance in Bifidobacterium breve. Bifidobacteria are mutualistic intestinal bacteria, and their presence in the human gut has been associated with health-promoting activities. The presence of antibiotic resistance genes in this genus is controversial, since, although bifidobacteria are nonpathogenic microorganisms, they could serve as reservoirs of resistance determinants for intestinal pathogens. However, until now, few antibiotic resistance determinants have been functionally characterized in this genus. In this work, we show that Bifidobacterium breve CECT7263 displays atypical resistance to erythromycin and clindamycin. In order to delimit the genomic region responsible for the observed resistance phenotype, a library of genomic DNA was constructed and a fragment of 5.8 kb containing a gene homologous to rRNA methylase genes was able to confer erythromycin resistance in Escherichia coli This genomic region seems to be very uncommon, and homologs of the gene have been detected in only one strain of Bifidobacterium longum and two other strains of B. breve In this context, analysis of shotgun metagenomics data sets revealed that the gene is also uncommon in the microbiomes of adults and infants. The structural gene and its upstream region were cloned into a B. breve-sensitive strain, which became resistant after acquiring the genetic material. In vitro conjugation experiments did not allow us to detect gene transfer to other recipients. Nevertheless, prediction of genes potentially acquired through horizontal gene transfer events revealed that the gene is located in a putative genomic island.IMPORTANCEBifidobacterium breve is a very common human intestinal bacterium. Often described as a pioneer microorganism in the establishment of early-life intestinal microbiota, its presence has been associated with several beneficial effects for the host, including immune stimulation and protection against infections. Therefore, some strains of this species are considered probiotics. In relation to this, because probiotic bacteria are used for human and animal consumption, one of the safety concerns over these bacteria is the presence of antibiotic resistance genes, since the human gut is a densely populated habitat that could favor the transfer of genetic material to potential pathogens. In this study, we analyzed the genetic basis responsible for the erythromycin and clindamycin resistance phenotype of B. breve CECT7263. We were able to identify and characterize a novel gene homologous to rRNA methylase genes which confers erythromycin and clindamycin resistance. This gene seems to be very uncommon in other bifidobacteria and in the gut microbiomes of both adults and infants. Even though conjugation experiments showed the absence of transferability under in vitro conditions, it has been predicted to be located in a putative genomic island recently acquired by specific bifidobacterial strains. | 2018 | 29500262 |