# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 4 | 0 | 0.9120 | Bacteria deplete deoxynucleotides to defend against bacteriophage infection. DNA viruses and retroviruses consume large quantities of deoxynucleotides (dNTPs) when replicating. The human antiviral factor SAMHD1 takes advantage of this vulnerability in the viral lifecycle, and inhibits viral replication by degrading dNTPs into their constituent deoxynucleosides and inorganic phosphate. Here, we report that bacteria use a similar strategy to defend against bacteriophage infection. We identify a family of defensive bacterial deoxycytidine triphosphate (dCTP) deaminase proteins that convert dCTP into deoxyuracil nucleotides in response to phage infection. We also identify a family of phage resistance genes that encode deoxyguanosine triphosphatase (dGTPase) enzymes, which degrade dGTP into phosphate-free deoxyguanosine and are distant homologues of human SAMHD1. Our results suggest that bacterial defensive proteins deplete specific deoxynucleotides (either dCTP or dGTP) from the nucleotide pool during phage infection, thus starving the phage of an essential DNA building block and halting its replication. Our study shows that manipulation of the dNTP pool is a potent antiviral strategy shared by both prokaryotes and eukaryotes. | 2022 | 35817891 |
| 105 | 1 | 0.9075 | Resistance of the cholera vaccine candidate IEM108 against CTXPhi infection. The cholera toxin (CT) genes ctxAB are carried on a lysogenic phage of Vibrio cholerae, CTXPhi, which can transfer ctxAB between toxigenic and nontoxigenic strains of bacteria. This transfer may pose a problem when live oral cholera vaccine is given to people in epidemic areas, because the toxin genes can be reacquired by the vaccine strains. To address this problem, we have constructed a live vaccine candidate, IEM108, which carries an El Tor-derived rstR gene. This gene encodes a repressor and can render bacterial resistance to CTXPhi infection. In this study, we evaluated the resistance of IEM108 against CTXPhi infection by using a CTXPhi marked for chloramphenicol (CAF) resistance and an in vivo model. We found that the cloned rstR gene rendered IEM108 immune to infection with the marked CTXPhi. In addition, the infection rate of IEM108 was even lower than that of the native CTXPhi-positive strain. These results suggest that the vaccine candidate IEM108 is resistant to infection by CTXPhi. | 2006 | 16343705 |
| 122 | 2 | 0.9056 | Functional characterization of ORCTL2--an organic cation transporter expressed in the renal proximal tubules. Chromosome 11p15.5 harbors a gene or genes involved in Beckwith-Wiedemann syndrome that confer(s) susceptibility to Wilms' tumor, rhabdomyosarcoma, and hepatoblastoma. We have previously identified a transcript at 11p15.5 which encodes a putative membrane transport protein, designated organic cation transporter-like 2 (ORCTL2), that shares homology with tetracycline resistance proteins and bacterial multidrug resistance proteins. In this report, we have investigated the transport properties of ORCTL2 and show that this protein can confer resistance to chloroquine and quinidine when overexpressed in bacteria. Immunohistochemistry analyses performed with anti-ORCTL2 polyclonal antibodies on human renal sections indicate that ORCTL2 is localized on the apical membrane surface of the proximal tubules. These results suggest that ORCTL2 may play a role in the transport of chloroquine and quinidine related compounds in the kidney. | 1998 | 9744804 |
| 110 | 3 | 0.9053 | Resistance to the macrolide antibiotic tylosin is conferred by single methylations at 23S rRNA nucleotides G748 and A2058 acting in synergy. The macrolide antibiotic tylosin has been used extensively in veterinary medicine and exerts potent antimicrobial activity against Gram-positive bacteria. Tylosin-synthesizing strains of the Gram-positive bacterium Streptomyces fradiae protect themselves from their own product by differential expression of four resistance determinants, tlrA, tlrB, tlrC, and tlrD. The tlrB and tlrD genes encode methyltransferases that add single methyl groups at 23S rRNA nucleotides G748 and A2058, respectively. Here we show that methylation by neither TlrB nor TlrD is sufficient on its own to give tylosin resistance, and resistance is conferred by the G748 and A2058 methylations acting together in synergy. This synergistic mechanism of resistance is specific for the macrolides tylosin and mycinamycin that possess sugars extending from the 5- and 14-positions of the macrolactone ring and is not observed for macrolides, such as carbomycin, spiramycin, and erythromycin, that have different constellations of sugars. The manner in which the G748 and A2058 methylations coincide with the glycosylation patterns of tylosin and mycinamycin reflects unambiguously how these macrolides fit into their binding site within the bacterial 50S ribosomal subunit. | 2002 | 12417742 |
| 5220 | 4 | 0.9048 | The first report of the vanC₁ gene in Enterococcus faecium isolated from a human clinical specimen. The vanC₁ gene, which is chromosomally located, confers resistance to vancomycin and serves as a species marker for Enterococcus gallinarum. Enterococcus faecium TJ4031 was isolated from a blood culture and harbours the vanC₁gene. Polymerase chain reaction (PCR) assays were performed to detect vanXYc and vanTc genes. Only the vanXYc gene was found in the E. faecium TJ4031 isolate. The minimum inhibitory concentrations of vancomycin and teicoplanin were 2 µg/mL and 1 µg/mL, respectively. Real-time reverse transcription-PCR results revealed that the vanC₁ and vanXYc genes were not expressed. Pulsed-field gel electrophoresis and southern hybridisation results showed that the vanC₁ gene was encoded in the chromosome. E. faecalis isolated from animals has been reported to harbour vanC₁gene. However, this study is the first to report the presence of the vanC₁gene in E. faecium of human origin. Additionally, our research showed the vanC₁gene cannot serve as a species-specific gene of E. gallinarum and that it is able to be transferred between bacteria. Although the resistance marker is not expressed in the strain, our results showed that E. faecium could acquire the vanC₁gene from different species. | 2014 | 25317698 |
| 5185 | 5 | 0.9045 | Genomic characterisation of nasal isolates of coagulase-negative Staphylococci from healthy medical students reveals novel Staphylococcal cassette chromosome mec elements. Coagulase-negative staphylococci (CoNS) are a diverse group of Gram-positive bacteria that are part of the normal human microbiota. Once thought to be non-pathogenic, CoNS has emerged in recent years as opportunistic pathogens of concern particularly in healthcare settings. In this study, the genomes of four methicillin-resistant CoNS isolates obtained from the nasal swabs of healthy university medical students in Malaysia were sequenced using the Illumina short-read platform. Genome sequencing enabled the identification of the four isolates as Staphylococcus warneri UTAR-CoNS1, Staphylococcus cohnii subsp. cohnii UTAR-CoNS6, Staphylococcus capitis subsp. urealyticus UTAR-CoNS20, and Staphylococcus haemolyticus UTAR-CoNS26. The genome of S. cohnnii UTAR-CoNS6 harboured the mecA methicillin-resistance gene on a Staphylococcal cassette chromosome mec (SCCmec) element similar to SCCmec type XIV (5 A) but the SCCmec cassettes identified in the other three CoNS genomes were novel and untypeable. Some of these SCCmec elements also encoded heavy metal resistance genes while the SCCmec type XIV (5 A) variant in S. cohnii UTAR-CoNS6 harboured the complete ica operon, a known virulence factor that functions in biofilm formation. In S. cohnii UTAR-CoNS6, the macrolide resistance genes msrA and mphC along with copper and cadmium resistance genes were located on a 26,630 bp plasmid, pUCNS6. This study showcased the diversity of CoNS in the nasal microbiota of medical students but the discovery of novel SCCmec elements, various antimicrobial and heavy metal resistance along with virulence genes in these isolates is of concern and warrants vigilance due to the likelihood of spread, especially to hospitalised patients. | 2025 | 40595841 |
| 5219 | 6 | 0.9043 | The first report of the vanC1 gene in Enterococcus faecium isolated from a human clinical specimen. The vanC1 gene, which is chromosomally located, confers resistance to vancomycin and serves as a species marker for Enterococcus gallinarum. Enterococcus faecium TJ4031 was isolated from a blood culture and harbours the vanC1gene. Polymerase chain reaction (PCR) assays were performed to detect vanXYc and vanTc genes. Only the vanXYc gene was found in the E. faecium TJ4031 isolate. The minimum inhibitory concentrations of vancomycin and teicoplanin were 2 µg/mL and 1 µg/mL, respectively. Real-time reverse transcription-PCR results revealed that the vanC1and vanXYc genes were not expressed. Pulsed-field gel electrophoresis and southern hybridisation results showed that the vanC1 gene was encoded in the chromosome. E. faecalis isolated from animals has been reported to harbour vanC1gene. However, this study is the first to report the presence of the vanC1gene in E. faecium of human origin. Additionally, our research showed the vanC1gene cannot serve as a species-specific gene of E. gallinarum and that it is able to be transferred between bacteria. Although the resistance marker is not expressed in the strain, our results showed that E. faecium could acquire the vanC1gene from different species. | 2014 | 25119395 |
| 3926 | 7 | 0.9040 | Could public restrooms be an environment for bacterial resistomes? Antibiotic resistance in bacteria remains a major problem and environments that help to maintain such resistance, represent a significant problem to infection control in the community. Restrooms have always been regarded as potential sources of infectious diseases and we suggest they have the potential to sustain bacterial "resistomes". Recent studies have demonstrated the wide range of different bacterial phyla that can be found in non-healthcare restrooms. In our study we focused on the Staphylococci. These species are often skin contaminants on man and have been reported as common restroom isolates in recent molecular studies. We collected samples from 18 toilets sited in 4 different public buildings. Using MALDI-TOF-MS and other techniques, we identified a wide range of antibiotic resistant Staphylococci and other bacteria from our samples. We identified 19 different Staphylococcal species within our isolates and 37.8% of the isolates were drug resistant. We also identified different Staphylococcal species with the same antibiograms inhabiting the same restrooms. Bacterial "resistomes" are communities of bacteria often localised in specific areas and within these environments drug resistance determinants may be freely transferred. Our study shows that non-healthcare restrooms are a source of antibiotic resistant bacteria where a collection of antibiotic resistance genes in pathogenic and non-pathogenic bacteria could form a resistome containing a "nexus of genetic diversity" | 2013 | 23349833 |
| 2 | 8 | 0.9037 | A Widespread Glycosidase Confers Lobophorin Resistance and Host-Dependent Structural Diversity. Identifying new environmental resistance determinants is significant to combat rising antibiotic resistance. Herein we report the unexpected correlation of a lobophorin (LOB) resistance-related glycosidase KijX with the host-dependent chemical diversity of LOBs, by a process of glycosylation, deglycosylation and reglycosylation. KijX homologues are widespread among bacteria, archaea and fungi, and encode the same glycohydrolytic activity on LOBs. The crystal structure of AcvX (a KijX homologue) shows a similar fold to that of the glycoside hydrolase family 113 and a special negatively charged groove to accommodate and deglycosylate LOBs. Antagonistic assays indicate kijX as a defense weapon of actinomycetes to combat LOB producers in environment, reflecting an elegant coevolution relationship. Our study provides insight into the KijX-related glycosidases as preexisting resistance determinants and represents an example of resistance genes accidentally integrated into natural product assembly. | 2023 | 37076762 |
| 6721 | 9 | 0.9035 | Aldehyde-resistant mycobacteria bacteria associated with the use of endoscope reprocessing systems. Bacteria can develop resistance to antibiotics, but little is known about their ability to increase resistance to chemical disinfectants. This study randomly sampled 3 automated endoscope reprocessors in the United States using aldehydes for endoscope disinfection. Bacterial contamination was found after disinfection in all automated endoscope reprocessors, and some mycobacteria isolates demonstrated significant resistance to glutaraldehyde and ortho-phthaldehyde disinfectants. Bacteria can survive aldehyde-based disinfection and may pose a cross-contamination risk to patients. | 2012 | 22325730 |
| 516 | 10 | 0.9034 | Role of Iron-Containing Alcohol Dehydrogenases in Acinetobacter baumannii ATCC 19606 Stress Resistance and Virulence. Most bacteria possess alcohol dehydrogenase (ADH) genes (Adh genes) to mitigate alcohol toxicity, but these genes have functions beyond alcohol degradation. Previous research has shown that ADH can modulate quorum sensing in Acinetobacter baumannii, a rising opportunistic pathogen. However, the number and nature of Adh genes in A. baumannii have not yet been fully characterized. We identified seven alcohol dehydrogenases (NAD(+)-ADHs) from A. baumannii ATCC 19606, and examined the roles of three iron-containing ADHs, ADH3, ADH4, and ADH6. Marker-less mutation was used to generate Adh3, Adh4, and Adh6 single, double, and triple mutants. Disrupted Adh4 mutants failed to grow in ethanol-, 1-butanol-, or 1-propanol-containing mediums, and recombinant ADH4 exhibited strongest activity against ethanol. Stress resistance assays with inorganic and organic hydroperoxides showed that Adh3 and Adh6 were key to oxidative stress resistance. Virulence assays performed on the Galleria mellonella model organism revealed that Adh4 mutants had comparable virulence to wild-type, while Adh3 and Adh6 mutants had reduced virulence. The results suggest that ADH4 is primarily involved in alcohol metabolism, while ADH3 and ADH6 are key to stress resistance and virulence. Further investigation into the roles of other ADHs in A. baumannii is warranted. | 2021 | 34576087 |
| 2401 | 11 | 0.9034 | Prevalence of vanC vancomycin-resistant enterococci in the teaching hospitals of the University of Debrecen, Hungary. Vancomycin-resistant enterococci (VRE) are common nosocomial pathogens; however, until now they have been rarely encountered in Hungary. In the present study, we investigated the prevalence of VRE in the teaching hospitals of the University of Debrecen. Of 7,271 Enterococcus-containing clinical samples collected between 2004 and 2009, we identified 16 VRE. Species-specific polymerase chain reaction was used to detect Enterococcus faecalis, Enterococcus faecium, Enterococcus casseliflavus, and Enterococcus gallinarum. Multiplex polymerase chain reaction was performed to identify the vancomycin resistance genes: vanA, vanB, vanC1/C2, vanD, vanE, and vanG. Restriction digestion with SalI and HindIII was introduced to differentiate the vanC1 and vanC2 genes from each other. Genetic relationships between the strains were investigated by pulsed-field gel electrophoresis. Overall, we identified the vanC1 resistance gene in 14 E. gallinarum and the vanC2 resistance gene in two E. casseliflavus strains. Except for two samples, the isolates had different pulsed-field gel electrophoresis types, suggesting sporadic emergence of the resistant bacteria. In addition, antibiotic resistance profile was determined by E-test. Three E. gallinarum strains proved to be resistant to gentamicin because of the presence of the aacA-aphD gene. Although the prevalence of VRE in Debrecen is rather low, the appearance of multiple resistances is of concern. | 2012 | 21649462 |
| 3670 | 12 | 0.9033 | Quantification of tetracycline and chloramphenicol resistance in digestive tracts of bulls and piglets fed with Toyocerin®, a feed additive containing Bacillus toyonensis spores. The complete genome sequencing of Bacillus toyonensis, the active ingredient of the feed additive Toyocerin(®), has revealed the presence of tetM and cat genes, a tetracycline and a chloramphenicol resistance gene, respectively. The aim of this study was to determine whether the use of Toyocerin(®) (viable spores of B. toyonensis) as a probiotic in feedstuff increased the abundance of tetracycline and chloramphenicol resistant bacteria in the intestinal tracts of piglets and Holstein bulls. To this end, qPCRs were designed to quantify the abundances of tetM and cat genes and B. toyonensis in the intestinal content of animals treated and non-treated with Toyocerin(®). Additionally, the culturable bacterial populations resistant to tetracycline or chloramphenicol were enumerated by plate counting. No statistical significances were detected between the concentrations of tetracycline or chloramphenicol resistant bacterial populations in treated and non-treated animals. The concentrations of tetM and cat in most of the treated animals were similar to those of B. toyonensis. Furthermore, tetM and cat genes were also detected in some non-treated animals, although in low concentrations. These results suggest that tetM and cat genes are already circulating among the commensal microbiota regardless of the use of Toyocerin(®). The use of Toyocerin(®) as a supplement in feedstuff does not increase the abundances of tetracycline and chloramphenicol resistant bacteria in the intestinal tracts of piglets and Holstein bulls beyond the contribution directly associated to the introduction of B. toyonensis spores through diet. | 2014 | 25085518 |
| 3655 | 13 | 0.9032 | Genetic Diversity and Antibiotic Resistance Among Coagulase-Negative Staphylococci Recovered from Birds of Prey in Portugal. Wild animal populations in contact with antimicrobials and antimicrobial resistant bacteria that are daily released into the environment are able to become unintentional hosts of these resistant microorganisms. To clarify this issue, our study evaluated the presence of antibiotic resistance determinants on coagulase-negative staphylococci recovered from birds of prey and studied their genetic relatedness by pulsed-field gel electrophoresis (PFGE). The unusual vga(A) and erm(T) genes, which confer resistance to clindamycin and erythromycin, respectively, were detected in Staphylococcus sciuri or Staphylococcus xylosus strains and the tet(K) gene in Staphylococcus kloosii. The PFGE patterns showed that three S. xylosus (isolated of Strix aluco and Otus scops) and two S. sciuri (recovered from Strix aluco and Milvus migrans) were clonally indistinguishable. These animals could be a source of unusual antimicrobial resistance determinants for highly used antibiotics in veterinary clinical practice. | 2016 | 26990729 |
| 101 | 14 | 0.9030 | The encapsulated strain TIGR4 of Streptococcus pneumoniae is phagocytosed but is resistant to intracellular killing by mouse microglia. The polysaccharide capsule is a major virulence factor of Streptococcus pneumoniae as it confers resistance to phagocytosis. The encapsulated serotype 4 TIGR4 strain was shown to be efficiently phagocytosed by the mouse microglial cell line BV2, whereas the type 3 HB565 strain resisted phagocytosis. Comparing survival after uptake of TIGR4 or its unencapsulated derivative FP23 in gentamicin protection and phagolysosome maturation assays, it was shown that TIGR4 was protected from intracellular killing. Pneumococcal capsular genes were up-regulated in intracellular TIGR4 bacteria recovered from microglial cells. Actual presence of bacteria inside BV2 cells was confirmed by transmission electron microscopy (TEM) for both TIGR4 and FP23 strains, but typical phagosomes/phagolysosomes were detected only in cells infected with the unencapsulated strain. In a mouse model of meningitis based on intracranic inoculation of pneumococci, TIGR4 caused lethal meningitis with an LD(50) of 2 × 10² CFU, whereas the LD(50) for the unencapsulated FP23 was greater than 10⁷ CFU. Phagocytosis of TIGR4 by microglia was also demonstrated by TEM and immunohistochemistry on brain samples from infected mice. The results indicate that encapsulation does not protect the TIGR4 strain from phagocytosis by microglia, while it affords resistance to intracellular killing. | 2010 | 20615478 |
| 6359 | 15 | 0.9028 | Drug resistance of oral bacteria to new antibacterial dental monomer dimethylaminohexadecyl methacrylate. Only two reports exist on drug-resistance of quaternary ammonium monomers against oral bacteria; both studies tested planktonic bacteria for 10 passages, and neither study tested biofilms or resins. The objectives of this study were to investigate the drug-resistance of Streptococcus mutans, Streptococcus sanguinis and Streptococcus gordonii against dimethylaminohexadecyl methacrylate (DMAHDM), and to evaluate biofilms on resins with repeated exposures for 20 passages for the first time. DMAHDM, dimethylaminododecyl methacrylate (DMADDM) and chlorhexidine (CHX) were tested with planktonic bacteria. Biofilms were grown on a resin containing 3% DMAHDM. Minimum-inhibitory concentrations were measured. To detect drug-resistance, the survived bacteria from the previous passage were used as inoculum for the next passage for repeated exposures. S. gordonii developed drug-resistance against DMADDM and CHX, but not against DMAHDM. Biofilm colony-forming units (CFU) on DMAHDM-resin was reduced by 3-4 log; there was no difference from passages 1 to 20 (p > 0.1). No drug-resistance to DMAHDM was detected for all three bacterial species. In conclusion, this study showed that DMAHDM induced no drug-resistance, and DMAHDM-resin reduced biofilm CFU by 3-4 log, with no significant change from 1 to 20 passages. DMAHDM with potent antibacterial activities and no drug-resistance is promising for dental applications. | 2018 | 29615732 |
| 5413 | 16 | 0.9028 | First detection of the staphylococcal trimethoprim resistance gene dfrK and the dfrK-carrying transposon Tn559 in enterococci. The trimethoprim resistance gene dfrK has been recently described in Staphylococcus aureus, but so far has not been found in other bacteria. A total of 166 enterococci of different species (E. faecium, E. faecalis, E. hirae, E. durans, E. gallinarum, and E. casseliflavus) and origins (food, clinical diseases in humans, healthy humans or animals, and sewage) were studied for their susceptibility to trimethoprim as determined by agar dilution (European Committee on Antimicrobial Susceptibility Testing) and the presence of (a) the dfrK gene and its genetic environment and (b) other dfr genes. The dfrK gene was detected in 49% of the enterococci (64% and 42% of isolates with minimum inhibitory concentrations of ≥2 mg/L or ≤1 mg/L, respectively). The tet(L)-dfrK linkage was detected in 21% of dfrK-positive enterococci. The chromosomal location of the dfrK gene was identified in one E. faecium isolate in which the dfrK was not linked to tet(L) gene but was part of a Tn559 element, which was integrated in the chromosomal radC gene. This Tn559 element was also found in 14 additional isolates. All combinations of dfr genes were detected among the isolates tested (dfrK, dfrG, dfrF, dfrK+dfrG, dfrK+dfrF, dfrF+dfrG, and dfrF+dfrG+dfrK). The gene dfrK gene was found together with other dfr genes in 58% of the tested enterococci. This study suggested an exchange of the trimethoprim resistance gene dfrK between enterococci and staphylococci, as previously observed for the trimethoprim resistance gene dfrG. | 2012 | 21718151 |
| 440 | 17 | 0.9028 | Nucleotide sequence analysis reveals similarities between proteins determining methylenomycin A resistance in Streptomyces and tetracycline resistance in eubacteria. Previous studies had localised the gene (mmr) for resistance to methylenomycin A (Mm) to a 2.5-kb PstI fragment in the middle of a cluster of Mm biosynthetic genes from the Streptomyces coelicolor plasmid SCP1. In this paper, the gene has been more precisely located by sub-cloning, and the nucleotide sequence of the whole fragment has been determined. The predicted mmr-specified protein (Mr 49238) would be hydrophobic, with some homology at the amino acid level to tetracycline-resistance proteins from both Gram-positive and Gram-negative bacteria. Comparisons of hydropathy plots of the amino acid sequences reinforces the idea that the proteins are similar. It is suggested that Mm resistance may be conferred by a membrane protein, perhaps controlling efflux of the antibiotic. No significant homology was detected by hybridisation analysis between mmr and a cloned oxytetracycline (OTc)-resistance gene (tetB) of the OTc producer Streptomyces rimosus, and no cross-resistance was conferred by these genes. Sequences on both sides of mmr appear to encode proteins. The direction of translation in each case would be opposite to that of mmr translation. This suggests that mmr is transcribed as a monocistronic mRNA from a bidirectional promoter. An extensive inverted repeat sequence between the stop codons of mmr and the converging gene may function as a bidirectional transcription terminator. | 1987 | 2828187 |
| 111 | 18 | 0.9026 | The tylosin resistance gene tlrB of Streptomyces fradiae encodes a methyltransferase that targets G748 in 23S rRNA. tlrB is one of four resistance genes encoded in the operon for biosynthesis of the macrolide tylosin in antibiotic-producing strains of Streptomyces fradiae. Introduction of tlrB into Streptomyces lividans similarly confers tylosin resistance. Biochemical analysis of the rRNA from the two Streptomyces species indicates that in vivo TlrB modifies nucleotide G748 within helix 35 of 23S rRNA. Purified recombinant TlrB retains its activity and specificity in vitro and modifies G748 in 23S rRNA as well as in a 74 nucleotide RNA containing helix 35 and surrounding structures. Modification is dependent on the presence of the methyl group donor, S-adenosyl methionine. Analysis of the 74-mer RNA substrate by biochemical and mass spectrometric methods shows that TlrB adds a single methyl group to the base of G748. Homologues of TlrB in other bacteria have been revealed through database searches, indicating that TlrB is the first member to be described in a new subclass of rRNA methyltransferases that are implicated in macrolide drug resistance. | 2000 | 10972803 |
| 400 | 19 | 0.9026 | The macrolide-lincosamide-streptogramin B resistance phenotypes characterized by using a specifically deleted, antibiotic-sensitive strain of Streptomyces lividans. Genes conferring resistance to macrolide, lincosamide, and streptogramin B (MLS) antibiotics via ribosomal modification are widespread in bacteria, including clinical isolates and MLS-producing actinomycetes. Such erm-type genes encode enzymes that mono- or dimethylate residue A-2058 of 23S rRNA. The different phenotypes resulting from monomethylation (MLS-I phenotype, conferred by erm type I genes) or dimethylation (MLS-II phenotype due to erm type II genes) have been characterized by introducing tlrD or ermE, respectively, into an MLS-sensitive derivative of Streptomyces lividans TK21. This strain (designated OS456) was generated by specific replacement of the endogenous resistance genes lrm and mgt. The MLS-I phenotype is characterized by high-level resistance to lincomycin with only marginal resistance to macrolides such as chalcomycin or tylosin, whereas the MLS-II phenotype involves high-level resistance to all MLS drugs. Mono- and dimethylated ribosomes were introduced into a cell-free protein-synthesizing system prepared from S. lividans and compared with unmodified particles in their response to antibiotics. There was no simple correlation between the relative potencies of MLS drugs at the level of the target site (i.e., the ribosome) and their antibacterial activities expressed as MICs. | 1996 | 8851574 |