The discovery of antibiotics is a big revolution in human history, and its clinical application has saved countless lives. However, with the widespread and abuse of antibiotics, many pathogens have developed resistance, and even "Super Bacteria" resistance to multiple drugs have evolved. In the arms race between humans and pathogens, humans are about to face a situation where no medicine is available. Research on microbial antibiotic resistance genes, resistance mechanisms, and the spread of resistance has attracted the attention of many scientific researchers, and various antibiotic resistance gene databases and analysis tools have emerged. In this review, we collect the current databases that focus on antibiotics resistance genes, and discuss these databases in terms of database types, data characteristics, antibiotics resistance gene prediction models and the types of analyzable sequences. In addition, a few gene databases of anti-metal ions and anti-biocides are also involved. It is believed that this summary will provide a reference for how to select and use antibiotic resistance gene databases.
Anti-Bacterial Agents/pharmacology* ; Bacterial Infections ; Drug Resistance, Bacterial/genetics* ; Drug Resistance, Microbial/genetics* ; Humans ; Metals

Forty-one strains of Streptococcus pneumoniae were isolated at Seoul National University Children's Hospital from 1991 to 1997. Isolates were divided into six groups based on MICs of three quinolones, ciprofloxacin, ofloxacin and norfloxacin. Sequencing showed that the isolates which were intermediately resistant to three quinolones or resistant to at least one kind of quinolone had one missense mutation, Lys137-->Asn(AAG-->AAT) substitution in the ParC subunit of topoisomerase IV without additional mutation in QRDR of the GyrA subunit of DNA gyrase. In conclusion, the ParC subunit of DNA topoisomerase IV is the primary target site for fluoroquinolone in S. pneumoniae and Lys137-->Asn substitution renders the quinolone resistance in S. pneumoniae.
DNA Topoisomerase (ATP-Hydrolysing)/genetics* ; Drug Resistance, Microbial/genetics* ; Human ; Isoenzymes/genetics* ; Mutation/genetics* ; Quinolones* ; Streptococcus pneumoniae/genetics

We analyzed the fluoroquinolone resistance mechanism of 28 isolates of ciprofloxacin-resistant E. coli from patients who received ciprofloxacin as a regimen of a selective gut decontamination. Isolates distinctive by infrequent restriction site polymerase chain reaction (IRS-PCR) were subjected to Hinf I restriction fragment length polymorphism analysis, single-stranded conformation polymorphism (SSCP), and nucleotide sequencing of the quinolone resistance determining region (QRDR) in gyrA. Double mutations in QRDR of gyrA (Ser83 Leu and Asp87Asn) were found from most of the strains. Nucleotide sequencing of the marR locus showed that 18 out of 28 (64%) ciprofloxacin-resistant E. coli strains had three types of base change in marR loci: a double-base change at nucleotides 1628 and 1751, or 1629 and 1751: and a single-base change at 1751. However, all the mutated strains showed no tolerance to cyclohexane test, suggesting the mutation in the marR region had no influence on overexpression of the MarA protein. In conclusion, mutation in gyrA was the main mechanism of ciporfloxacin resistance in E. coli from patients with selective gut decontamination. Therefore, mutation in the mar region did not influence the levels of ciprofloxacin resistance in our isolates.
Ciprofloxacin/pharmacology* ; DNA Topoisomerase (ATP-Hydrolysing)/genetics* ; Drug Resistance, Microbial/genetics* ; Drug Resistance, Multiple/genetics* ; Escherichia coli/genetics ; Escherichia coli/drug effects* ; Human ; Mutation/physiology

OBJECTIVETo investigate antibiotic resistance and carriage class 1 and 2 integrons in clinical isolates of Acinetobacter baumannii (A. baumannii) from Tehran, Iran.

METHODSAntimicrobial susceptibility testing was performed according to the Clinical and Laboratory Standards Institute. The presence of integrons was investigated by PCR using specific primers.

RESULTSAmong isolated A. baumannii strains, 82% were multidrug resistant, 27 samples (54%) were resistant to three or more than three antibiotics and 16 samples (32%) showed resistance to two antibiotics. Integrons were detected from 44 of 50 isolates (88%), with classes 1 and 2 being observed in 42% (21/50) and 82% (41/50) of isolates, respectively. Integron-positive A. baumannii isolates showed higher antibiotic resistance than integron-negative isolates and all showed a multidrug-resistant phenotype.

CONCLUSIONSOur findings show that classes 1 and 2 integrons, and especially classes 2 integrons are widely disseminated among A. baumannii strains isolated from Tehran and these structures are playing a major role in the acquisition of multidrug resistance in these strains. So monitoring of drug resistance with investigating carriage class 1 and 2 integrons is very important to plan specific infection control measures due to multidrug resistance A. baumannii in Iran hospitals.

Acinetobacter baumannii ; drug effects ; genetics ; Anti-Bacterial Agents ; pharmacology ; Drug Resistance, Multiple, Bacterial ; genetics ; Integrons ; genetics ; Iran ; Microbial Sensitivity Tests

Objective: To explore the changes in bacterial community structure, antibiotic resistance genome, and pathogen virulence genome in river water before and after the river flowing through Haikou City and their transmission and dispersal patterns and to reveal anthropogenic disturbance's effects on microorganisms and resistance genes in the aquatic environment. Methods: The Nandu River was divided into three study areas: the front, middle and rear sections from the upstream before it flowed through Haikou City to the estuary. Three sampling sites were selected in each area, and six copies of the sample were collected in parallel at each site and mixed for 3 L per sample. Microbial community structure, antibiotic resistance, virulence factors, and mobile genetic elements were analyzed through bioinformatic data obtained by metagenomic sequencing and full-length sequencing of 16S rRNA genes. Variations in the distribution of bacterial communities between samples and correlation of transmission patterns were analyzed by principal co-ordinates analysis, procrustes analysis, and Mantel test. Results: As the river flowed through Haikou City, microbes' alpha diversity gradually decreased. Among them, Proteobacteria dominates in the bacterial community in the front, middle, and rear sections, and the relative abundance of Proteobacteria in the middle and rear sections was higher than that in the front segment. The diversity and abundance of antibiotic resistance genes, virulence factors, and mobile genetic elements were all at low levels in the front section and all increased significantly after flow through Haikou City. At the same time, horizontal transmission mediated by mobile genetic elements played a more significant role in the spread of antibiotic-resistance genes and virulence factors. Conclusions: Urbanization significantly impacts river bacteria and the resistance genes, virulence factors, and mobile genetic elements they carry. The Nandu River in Haikou flows through the city, receiving antibiotic-resistant and pathogen-associated bacteria excreted by the population. In contrast, antibiotic-resistant genes and virulence factors are enriched in bacteria, which indicates a threat to environmental health and public health. Comparison of river microbiomes and antibiotic resistance genomes before and after flow through cities is a valuable early warning indicator for monitoring the spread of antibiotic resistance.
Humans ; Rivers ; Virulence Factors/genetics* ; RNA, Ribosomal, 16S/genetics* ; Microbiota/genetics* ; Anti-Bacterial Agents ; Drug Resistance, Microbial/genetics*

OBJECTIVETuberculosis remains a severe public health issue, and the Beijing family of mycobacterium tuberculosis (M. tuberculosis) is widespread in East Asia, especially in some areas in China, like Beijing and Tianjin. This study aimed at determining the mutation patterns of drug-resistant Beijing strains of M. tuberculosis isolated from Tianjin, China.

METHODSA total of 822 M. tuberculosis isolates were screened for drug resistance by an absolute concentration method and the genotype was identified by PCR. 169 drug-resistant isolates of the Beijing family were analyzed for the potential mutations in the rpoB, katG, inhA promoter region and in rpsL, rrs and embB genes, which are associated with resistance to rifampin (RFP), isoniazid (INH), streptomycin (SM) and ethambutol (EMB) respectively by PCR and DNA sequencing.

RESULTSFifty-eight out of 63 RFP-resistant isolates were found to carry the mutations within the 81-bp RFP resistance determining region (RRDR) of the rpoB gene and the most frequent mutations occurred at codon 531 (44.4%), 526 (28.6%), and 516 (7.9%) respectively. 16 mutation patterns affecting 12 different codons around the RRDR of rpoB were found. Of 116 INH-resistant isolates, 56 (48.3%) had the mutation of katG 315 (AGC-->ACC) (Ser-->Thr), 3 (2.6%) carried S315N (AGC-->AAC) and 27 (16.0%) had the mutation of inhA-15A-->T. 84 out of 122 SM-resistant isolates (68.9%) displayed mutations at the codons 43 or 88 with AAG-->AGG (Lys-->Arg) of the rpsL gene and 22 (18.0%) with the mutations at positions 513A-->C, 516C-->T or 905 A-->G in the rrs gene. Of 34 EMB-resistant isolates, 6 had mutation with M306V (ATG-->GTG), 3 with M306I (ATG-->ATT), 1 with M306I (ATG-->ATA), 1 with D328Y (GAT-->TAT), 1 with V348L (GTC-->CTC), and 1 with G406S (GGC-->AGC) in the embB gene.

CONCLUSIONThese novel findings extended our understanding of resistance-related mutations in the Beijing strains of M. tuberculosis and may provide a scientific basis for development of new strategies for diagnosis and control of tuberculosis in China and other countries where Beijing strains are prevalent.

Base Sequence ; China ; DNA Primers ; Drug Resistance, Microbial ; Mycobacterium tuberculosis ; genetics ; Polymerase Chain Reaction

Antibiotic resistance is a major global concern and challenge in the 21st century. Enterobacteriaceae are one of the important pathogens of hospital-acquired infections. With the increasing use of antibiotics in clinical practice, a variety of drug-resistant Enterobacteriaceae, especially multidrug-resistant Enterobacteriaceae have emerged, posing an increasingly serious threat to human health. Bacteria can acquire antibiotic resistance by mutation or horizontal transfer of antibiotic resistance genes, and it is often possible to predict the corresponding resistance phenotype from known mechanism. However, recent findings suggest that genetic background and environmental factors could alter the expression of specific resistance genes and that a given genotype does not always generate the expected resistance phenotype. The genotype-phenotype segregation greatly hampers our ability to predict antibiotic resistance phenotype from a genetic perspective. In this review, we explore the genetic and environmental regulation of the expression of antibiotic resistance genes in a variety of Enterobacteriaceae, with the aim to provide scientific evidence for genetic prediction of antibiotic resistance phenotype and clinical guidance on drug use.
Anti-Bacterial Agents/pharmacology* ; Bacteria ; Cross Infection ; Drug Resistance, Microbial ; Enterobacteriaceae/genetics* ; Humans

Resistome is a cluster of microbial genes encoding proteins with necessary functions to resist the action of antibiotics. Resistome governs essential and separate biological functions to develop resistance against antibiotics. The widespread clinical and nonclinical uses of antibiotics over the years have combined to select antibiotic-resistant determinants and develop resistome in bacteria. At present, the emergence of drug resistance because of resistome is a significant problem faced by clinicians for the treatment of Salmonella infection. Antibiotic resistome is a dynamic and ever-expanding component in Salmonella. The foundation of resistome in Salmonella is laid long before; therefore, the antibiotic resistome of Salmonella is reviewed, discussed, and summarized. We have searched the literature using PubMed, MEDLINE, and Google Scholar with related key terms (resistome, Salmonella, antibiotics, drug resistance) and prepared this review. In this review, we summarize the status of resistance against antibiotics in S. typhi, highlight the seminal work in the resistome of S. typhi and the genes involved in the antibiotic resistance, and discuss the various methods to identify S. typhi resistome for the proactive identification of this infection and quick diagnosis of the disease.
Anti-Bacterial Agents/pharmacology* ; Drug Resistance ; Humans ; Microbial Sensitivity Tests ; Salmonella ; Salmonella typhi/genetics*

Antitubercular Agents ; pharmacology ; Drug Resistance, Multiple, Bacterial ; genetics ; Humans ; Microbial Sensitivity Tests ; methods ; Mycobacterium tuberculosis ; drug effects ; genetics

OBJECTIVETo construct double gene deletions at the htrA and clpP loci on the chromosome of Streptococcus mutans (Sm) and to remove the antibiotic resistance markers with the Cre-loxP(*) site-specific recombination system.

METHODSThe htrA gene was cloned into the pGEM-T-Easy TA cloning vector and then inactivated via the insertion of a kanamycin resistance cassette (lox71-Km-lox66), yielding pGEM-T-ΔhtrA/Km for deleting the htrA gene. Using the same method, the pGEM-T-ΔclpP/Sp was constructed for deleting the clpP gene. Following the transformation of pGEM-T-ΔhtrA/Km in Sm, the homologous recombination event was selected. One such mutant was transformed with a cre expression plasmid (pCrePA). The kanamycin resistance gene was then excised. The pCrePA was then easily eliminated at nonpermissive temperatures, resulting in a mutant strain (MSΔhtrA) carrying a deletion at the htrA loci without a selectable marker. This mutant was verified by PCR and DNA sequencing. Then, the clpP and spectinomycin resistance gene were deleted from MSΔhtrA, yielding markerless mutant strain lacking clpP and htrA.

RESULTSThe deletion of htrA, clpP and antibiotic resistance markers were confirmed by PCR analysis and DNA sequencing.

CONCLUSIONSA mutant of Sm was constructed successfully which contained a deletion of the htrA and clpP gene without selectable marker. The Cre-loxP(*) system can be applied to Sm, which provides experimental evidence for generating markerless multiple gene deletion mutants.

Drug Resistance, Microbial ; genetics ; Gene Deletion ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Genetic Vectors ; Integrases ; genetics ; Plasmids ; Streptococcus mutans ; genetics