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1.
Trop Anim Health Prod ; 56(4): 160, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730050

ABSTRACT

The rearing of calves is an essential activity of a dairy system, as it impacts the future production of these animals. This study aims to evaluate the incidence of diarrhea, performance, and blood parameters of suckling calves that received mineral-vitamin supplementation in milk plus virginiamycin that was offered in milk (via the abomasum) or by esophageal tube (via the rumen). Twenty-seven calves were used, from the first week to 60 days of age, submitted to the following treatments: CONTROL, without supplementation; MILK, supplementation of 20 g of a mineral-vitamin complex with 100 mg of virginiamycin, diluted in milk; RUMEN, supplementation of 20 g of a mineral-vitamin complex diluted in milk and 100 mg of virginiamycin in gelatin capsules via an esophageal applicator. MILK and RUMEN calves had lower fecal consistency scoring, fewer days with scores 2 and 3 throughout the experimental period, and lower spending on medication compared to the CONTROL animals. Supplemented calves had higher fat and protein intake and reached feed intake of 600 g earlier than CONTROL animals, but did not differ in performance and hematological parameters. Supplementation with virginiamycin and vitamin-mineral complex for suckling calves reduced the incidence and days of diarrhea, and reduced medication costs, with no difference in performance, but the supplemented animals had higher initial protein and fat intake and reached targeted feed intake earlier to begin the weaning process.


Subject(s)
Animal Feed , Cattle Diseases , Diarrhea , Dietary Supplements , Virginiamycin , Animals , Cattle , Dietary Supplements/analysis , Diarrhea/veterinary , Diarrhea/prevention & control , Diarrhea/epidemiology , Cattle Diseases/epidemiology , Cattle Diseases/prevention & control , Incidence , Animal Feed/analysis , Virginiamycin/administration & dosage , Virginiamycin/pharmacology , Vitamins/administration & dosage , Animals, Suckling , Male , Female , Minerals/administration & dosage , Minerals/analysis , Milk/chemistry , Diet/veterinary
2.
Acc Chem Res ; 54(8): 1891-1908, 2021 04 20.
Article in English | MEDLINE | ID: mdl-33792282

ABSTRACT

Continued, rapid development of antimicrobial resistance has become worldwide health crisis and a burden on the global economy. Decisive and comprehensive action is required to slow down the spread of antibiotic resistance, including increased investment in antibiotic discovery, sustainable policies that provide returns on investment for newly launched antibiotics, and public education to reduce the overusage of antibiotics, especially in livestock and agriculture. Without significant changes in the current antibiotic pipeline, we are in danger of entering a post-antibiotic era.In this Account, we summarize our recent efforts to develop next-generation streptogramin and lankacidin antibiotics that overcome bacterial resistance by means of modular chemical synthesis. First, we describe our highly modular, scalable route to four natural group A streptogramins antibiotics in 6-8 steps from seven simple chemical building blocks. We next describe the application of this route to the synthesis of a novel library of streptogramin antibiotics informed by in vitro and in vivo biological evaluation and high-resolution cryo-electron microscopy. One lead compound showed excellent inhibitory activity in vitro and in vivo against a longstanding streptogramin-resistance mechanism, virginiamycin acetyltransferase. Our results demonstrate that the combination of rational design and modular chemical synthesis can revitalize classes of antibiotics that are limited by naturally arising resistance mechanisms.Second, we recount our modular approaches toward lankacidin antibiotics. Lankacidins are a group of polyketide natural products with activity against several strains of Gram-positive bacteria but have not been deployed as therapeutics due to their chemical instability. We describe a route to several diastereomers of 2,18-seco-lankacidinol B in a linear sequence of ≤8 steps from simple building blocks, resulting in a revision of the C4 stereochemistry. We next detail our modular synthesis of several diastereoisomers of iso-lankacidinol that resulted in the structural reassignment of this natural product. These structural revisions raise interesting questions about the biosynthetic origin of lankacidins, all of which possessed uniform stereochemistry prior to these findings. Finally, we summarize the ability of several iso- and seco-lankacidins to inhibit the growth of bacteria and to inhibit translation in vitro, providing important insights into structure-function relationships for the class.


Subject(s)
Anti-Bacterial Agents/chemical synthesis , Macrolides/chemical synthesis , Streptogramins/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/drug effects , Escherichia coli/metabolism , Gram-Negative Bacteria , Gram-Positive Bacteria/drug effects , Macrolides/chemistry , Macrolides/pharmacology , Microbial Sensitivity Tests , Molecular Conformation , Molecular Dynamics Simulation , Ribosomes/chemistry , Ribosomes/metabolism , Streptogramins/chemistry , Streptogramins/pharmacology , Virginiamycin/analogs & derivatives , Virginiamycin/chemical synthesis , Virginiamycin/metabolism , Virginiamycin/pharmacology
3.
Lett Appl Microbiol ; 74(5): 831-838, 2022 May.
Article in English | MEDLINE | ID: mdl-35138674

ABSTRACT

Considering that plasmid conjugation is a major driver for the dissemination of antimicrobial resistance in bacteria, this study aimed to investigate the effects of residual concentrations of antimicrobial growth promoters (AGPs) in poultry litter on the frequencies of IncFII-FIB plasmid conjugation among Escherichia coli organisms. A 2 × 5 factorial trial was performed in vitro, using two types of litter materials (sugarcane bagasse and wood shavings) and five treatments of litter: non-treated (CON), herbal alkaloid sanguinarine (SANG), AGPs monensin (MON), lincomycin (LCM) and virginiamycin (VIR). E. coli H2332 and E. coli J62 were used as donor and recipient strains, respectively. The presence of residues of monensin, lincomycin and virginiamycin increased the frequency of plasmid conjugation among E. coli in both types of litter materials. On the contrary, sanguinarine significantly reduced the frequency of conjugation among E. coli in sugarcane bagasse litter. The conjugation frequencies were significantly higher in wood shavings compared with sugarcane bagasse only in the presence of AGPs. Considering that the presence of AGPs in the litter can increase the conjugation of IncFII-FIB plasmids carrying antimicrobial resistance genes, the real impact of this phenomenon on the dissemination of antimicrobial resistant bacteria in the poultry production chain must be investigated.


Subject(s)
Anti-Infective Agents , Escherichia coli Infections , Saccharum , Animals , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Cellulose/pharmacology , Conjugation, Genetic , Escherichia coli/genetics , Escherichia coli Infections/microbiology , Lincomycin/pharmacology , Monensin , Plasmids/genetics , Poultry/microbiology , Virginiamycin/pharmacology
4.
Environ Microbiol ; 22(7): 2858-2869, 2020 07.
Article in English | MEDLINE | ID: mdl-32291839

ABSTRACT

The use of mass antimicrobial treatment has been linked to the emergence of antimicrobial resistance in human and animal pathogens. Using whole-genome single-molecule real-time (SMRT) sequencing, we characterized genomic variability of multidrug-resistant Rhodococcus equi isolated from soil samples from 100 farms endemic for R. equi infections in Kentucky. We discovered the novel erm(51)-encoding resistance to MLSB in R. equi isolates from soil of horse-breeding farms. Erm(51) is inserted in a transposon (TnErm51) that is associated with a putative conjugative plasmid (pRErm51), a mobilizable plasmid (pMobErm51), or both enabling horizontal gene transfer to susceptible organisms and conferring high levels of resistance against MLSB in vitro. This new resistant genotype also carries a previously unidentified rpoB mutation conferring resistance to rifampicin. Isolates carrying both vapA and erm(51) were rarely found, indicating either a recent acquisition of erm(51) and/or impaired survival when isolates carry both genes. Isolates carrying erm(51) are closely related genetically and were likely selected by antimicrobial exposure in the environment.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Rhodococcus equi/drug effects , Rhodococcus equi/genetics , Animals , DNA Transposable Elements/genetics , Farms , Gene Transfer, Horizontal , Genome, Bacterial/genetics , Horses , Lincosamides/pharmacology , Macrolides/pharmacology , Microbial Sensitivity Tests , Plasmids/genetics , Streptogramin B/pharmacology , Streptogramin Group B/pharmacology , Virginiamycin/pharmacology
5.
Molecules ; 25(23)2020 Dec 03.
Article in English | MEDLINE | ID: mdl-33287389

ABSTRACT

The ability of Staphylococcus epidermidis to produce virulence factors, such as biofilm, added to its increased resistance to antimicrobials can cause infections that are difficult to treat. Many staphylococcal virulence factors are under the control of the accessory gene regulator (agr). The objective of this study was to establish the agr locus and susceptibility of biofilm-producing S. epidermidis specimens to antimicrobial agents, through PCR reactions, reverse transcription polymerase chain reaction (RT-PCR), and the determination of minimum inhibitory concentration (MIC), and to analyze the clonal profile of 300 strains isolated from blood culture specimens from inpatients at a University Hospital in Brazil, over a 20-year period by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) techniques. The ica operon expression was shown in 83.6% strains, bhp gene in 11.5%, and aap gene in 32.8%. Oxacillin resistance was detected in 90.1%, while 4.9% showed tigecycline resistance, and intermediate resistance to quinupristin/dalfopristin was identified in 0.4%. Clonal profile determination showed 11 clusters, with the ST2 type determined as the major cluster. The S. epidermidis biofilm producer demonstrated a predominance of agr I locus, oxacillin resistance, and SCCmec III as well as the potential dissemination of pathogenic clones in hospital settings over long periods.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Biofilms/drug effects , Drug Resistance, Bacterial/drug effects , Staphylococcal Infections/drug therapy , Staphylococcus epidermidis/drug effects , Staphylococcus epidermidis/metabolism , Brazil , Electrophoresis, Gel, Pulsed-Field/methods , Humans , Microbial Sensitivity Tests/methods , Multilocus Sequence Typing/methods , Staphylococcal Infections/microbiology , Virginiamycin/pharmacology
6.
World J Microbiol Biotechnol ; 35(4): 66, 2019 Apr 02.
Article in English | MEDLINE | ID: mdl-30941513

ABSTRACT

It is widely assumed that bacterial resistance will be acquired when bacteria are exposed to long-term sublethal concentrations of antibiotics. The objective of this study was to evaluate the ability of two bacterial strains [Lactobacillus plantarum (18A) and Lactobacillus paracasei (18C)] isolated from the fuel ethanol industry to acquire bacterial resistance during long-term (≥ 14 days) exposure to sublethal concentrations of penicillin G and virginiamycin. Neither strain acquired resistance to virginiamycin after 69 days of exposure, but both strains did acquire resistance to penicillin G after 18 days. Strain 18A appeared to acquire resistance to a penicillin G and virginiamycin mixture after 7 days of exposure, but the incubation period was not long enough to verify. These results indicate that antibiotic resistance in two common Lactobacillus strains does not develop from sublethal exposure to virginiamycin after 69 days of exposure, but resistance can be developed with sublethal exposure to penicillin G.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Bacteria/metabolism , Drug Resistance, Bacterial/drug effects , Ethanol/metabolism , Bacteria/growth & development , Bacteria/isolation & purification , Biofuels , Fermentation , Lacticaseibacillus paracasei/drug effects , Lacticaseibacillus paracasei/growth & development , Lacticaseibacillus paracasei/isolation & purification , Lacticaseibacillus paracasei/metabolism , Lactobacillus plantarum/drug effects , Lactobacillus plantarum/growth & development , Lactobacillus plantarum/isolation & purification , Lactobacillus plantarum/metabolism , Microbial Sensitivity Tests , Models, Theoretical , Penicillin G/pharmacology , Virginiamycin/pharmacology
7.
J Antimicrob Chemother ; 73(1): 33-40, 2018 Jan 01.
Article in English | MEDLINE | ID: mdl-29048488

ABSTRACT

OBJECTIVES: Clonal complex (CC) 9 is a prevalent livestock-associated (LA) MRSA clone in Asia whose pathogenicity in humans remains unknown. METHODS: In 2012, we identified a patient with CC9-MRSA infection linked to livestock. After screening 3328 clinical MRSA isolates from a national database, eight isolates (0.24%) collected between 1998 and 2012 were further confirmed to be of CC9. The detailed molecular features of the nine human CC9 strains and phylogenetic relatedness to animal CC9 strains were characterized with WGS. The antibiotic susceptibilities were determined and the clinical information was abstracted from medical records. RESULTS: WGS grouped the CC9 strains into two clades, which were respectively associated with distinct toxome profiles, resistance gene profiles and staphylococcal cassette chromosomes (SCCmecXII for 7 isolates and SCCmecVT for 2 isolates). The SCCmecXII strains were phylogenetically related to animal CC9-MRSA strains, negative for Panton-Valentine leucocidin and 100% resistant to ciprofloxacin, erythromycin, clindamycin, gentamicin and tigecycline. Four of the seven SCCmecXII isolates were associated with invasive diseases including bacteraemia leading to death (2) and osteomyelitis (2). Two SCCmecXII isolates were from patients with exposure to pigs before development of the MRSA diseases. CONCLUSIONS: The CC9-SCCmecXII MRSA prevailing in pigs in Asia is multidrug resistant and potentially pathogenic to humans. It is critical to continuously monitor the local epidemiology of MRSA and implement effective control measures to limit the spread of LA-MRSA between animals, to humans and in healthcare facilities.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial/genetics , Livestock/microbiology , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections/drug therapy , Staphylococcal Infections/transmission , Adult , Aged , Aged, 80 and over , Animals , Child, Preschool , Ciprofloxacin/pharmacology , Clindamycin/pharmacology , Erythromycin/pharmacology , Farmers , Female , Gentamicins/pharmacology , Humans , Male , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Microbial Sensitivity Tests , Middle Aged , Minocycline/analogs & derivatives , Minocycline/pharmacology , Staphylococcal Infections/microbiology , Swine , Swine Diseases/microbiology , Swine Diseases/transmission , Taiwan , Tigecycline , Virginiamycin/pharmacology , beta-Lactam Resistance/genetics , beta-Lactams/pharmacology
8.
Eur J Clin Microbiol Infect Dis ; 37(5): 959-967, 2018 May.
Article in English | MEDLINE | ID: mdl-29478197

ABSTRACT

High-throughput sequencing (HTS) has successfully identified novel resistance genes in enterococci and determined clonal relatedness in outbreak analysis. We report the use of HTS to investigate two concurrent outbreaks of glycopeptide-resistant Enterococcus faecium (GRE) with an uncharacterised resistance mechanism to quinupristin-dalfopristin (QD). Seven QD-resistant and five QD-susceptible GRE isolates from a two-centre outbreak were studied. HTS was performed to identify genes or predicted proteins that were associated with the QD-resistant phenotype. MLST and SNP typing on HTS data was used to determine clonal relatedness. Comparative genomic analysis confirmed this GRE outbreak involved two distinct clones (ST80 and ST192). HTS confirmed the absence of known QD resistance genes, suggesting a novel mechanism was conferring resistance. Genomic analysis identified two significant genetic determinants with explanatory power for the high level of QD resistance in the ST80 QD-resistant clone: an additional 56aa leader sequence at the N-terminus of the lsaE gene and a transposon containing seven genes encoding proteins with possible drug or drug-target modification activities. However, HTS was unable to conclusively determine the QD resistance mechanism and did not reveal any genetic basis for QD resistance in the ST192 clone. This study highlights the usefulness of HTS in deciphering the degree of relatedness in two concurrent GRE outbreaks. Although HTS was able to reveal some genetic candidates for uncharacterised QD resistance, this study demonstrates the limitations of HTS as a tool for identifying putative determinants of resistance to QD.


Subject(s)
Anti-Bacterial Agents/pharmacology , Disease Outbreaks , Drug Resistance, Bacterial , Enterococcus faecium/drug effects , Glycopeptides/pharmacology , Gram-Positive Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/microbiology , Virginiamycin/pharmacology , Enterococcus faecium/classification , Enterococcus faecium/genetics , Genes, Bacterial , High-Throughput Nucleotide Sequencing , Humans , Microbial Sensitivity Tests , Multilocus Sequence Typing , Phylogeny , Polymorphism, Single Nucleotide
9.
Int J Med Microbiol ; 306(8): 722-729, 2016 12.
Article in English | MEDLINE | ID: mdl-27528592

ABSTRACT

Whole-genome sequencing (WGS) was used to investigate the genetic features of the recently identified lsa(E) gene in porcine S. aureus ST9 isolates. Three quinupristin/dalfopristin-resistant isolates harboring the lsa(E) gene (two MRSA and one MSSA) were sequenced. Phylogenetic analysis of 184S. aureus genomes showed that ST9 porcine isolates belong to a distinct sequence cluster. Further analysis showed that all isolates were deficient in the recently described type IV restriction-modification system and SCCmec type XII was identified in the two MRSA isolates, which included a rare class C2 mec gene complex. A 24kb ΨSCC fragment was found in the MRSA and MSSA isolates sharing 99% nucleotide sequence homology with the ΨSCCJCSC6690 (O-2) element of a ST9 MRSA isolate from Thailand (accession number AB705453). Comparison of these ST9 isolates with 181 publically available S. aureus genomes identified 24 genes present in all (100%) ST9 isolates, that were absent from the most closely related human isolate. Our analysis suggests that the sequenced quinupristin/dalfopristin-resistant ST9 lineage represent a reservoir of mobile genetic elements associated with resistance and virulence features.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Genes, Bacterial , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purification , Swine/microbiology , Virginiamycin/pharmacology , Animals , Cluster Analysis , DNA Restriction-Modification Enzymes/deficiency , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Gene Order , Genome, Bacterial , Genotype , Interspersed Repetitive Sequences , Molecular Typing , Phylogeny , Sequence Analysis, DNA , Sequence Homology , Staphylococcus aureus/classification , Thailand
10.
BMC Microbiol ; 16(1): 246, 2016 10 21.
Article in English | MEDLINE | ID: mdl-27769188

ABSTRACT

BACKGROUND: Quinupristin/dalfopristin (Q/D) is a valuable alternative antibiotic to vancomycin for the treatment of multi-drug resistant Enterococcus faecium infections. However, resistance to Q/D in E. faecium clinical isolates and nosocomial dissemination of Q/D-resistant E. faecium have been reported in several countries and should be of concern. RESULTS: From January 2012 to December 2015, 911 E. faecium clinical isolates were isolated from various specimens of inpatients at the first Affiliated Hospital of Wenzhou Medical University located in Wenzhou, east China. Of 911 E. faecium clinical isolates, 9 (1.0 %, 9/911) were resistant to Q/D, with the Q/D MIC values of 64 mg/L(1), 32 mg/L(1), 16 mg/L(3), 8 mg/L(1) and 4 mg/L(3) determined by broth microdilution. All Q/D-resistant isolates were susceptible to vancomycin, tigecycline and teicoplanin but resistant to penicillin, ampicillin and erythromycin. vatE was only found in one Q/D-resistant E. faecium isolate while vatD was not detected in any of the isolates tested. 8 of 9 Q/D-resistant E. faecium isolates were found be positive for both ermB and msrC. The combinations of Q/D resistance determinants were ermB-msrC (7 isolates) and ermB-msrC-vatE (one isolate). ST78, ST761, ST94, ST21 and ST323 accounted for 4, 2, 1, 1 and 1 isolate, respectively, among which ST78 was the prevalent ST. CONCLUSION: Q/D-resistant E. faecium clinical isolates were first described in China. Carriage of vatE, ermB and msrC was responsible for Q/D resistance.


Subject(s)
Anti-Bacterial Agents/pharmacology , Enterococcus faecium/drug effects , Enterococcus faecium/isolation & purification , Gram-Positive Bacterial Infections/microbiology , Virginiamycin/pharmacology , Bacterial Proteins/genetics , China/epidemiology , Cross Infection , DNA, Bacterial/genetics , Drug Resistance, Multiple, Bacterial , Enterococcus faecium/genetics , Genes, Bacterial , Gram-Positive Bacterial Infections/epidemiology , Humans , Microbial Sensitivity Tests , Multilocus Sequence Typing/methods , Prevalence , RNA, Ribosomal, 16S/genetics , Vancomycin/pharmacology
11.
Appl Microbiol Biotechnol ; 100(11): 5045-57, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26921181

ABSTRACT

This work is the first to report the antibacterial characteristics and antibacterial mechanisms of MP1102, which is a variant of NZ2114, against pathogenic Clostridium perfringens. MP1102 exhibited strong antimicrobial activity against C. perfringens strains CVCC 61, CVCC 1163, and CVCC 2032 at a low minimal inhibitory concentration (MIC) of 0.91 µM. MP1102 showed anti-C. perfringens activity over a wide pH range of 2.0 and 10.0, high thermal stability from 20 to 80 °C, and remarkable resistance to pepsin. The fractional inhibitory concentration index (FICI) indicated an additive or synergic effect between MP1102 and bacitracin zinc, nisin, vancomycin, virginiamycin, aureomycin, and ampicillin against C. perfringens (FICI = 0.3125-1.0). To further elucidate the antibacterial mechanism of MP1102, its effect on the C. perfringens CVCC 61 cell membrane and intracellular DNA was studied. Flow cytometry and scanning electron microscopy (SEM) indicated that MP1102 treatment resulted in the release of cellular contents by damaging the membrane. A DNA gel retardation and circular dichroism analysis demonstrated that MP1102 interacted with DNA and intercalated into the DNA base pairs. A cell cycle assay demonstrated that MP1102 affected cellular functions, such as DNA synthesis. These results suggested that MP1102 exhibited potential as a new antimicrobial agent against C. perfringens infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Clostridium perfringens/drug effects , Recombinant Proteins/pharmacology , Ampicillin/pharmacology , Cell Membrane/drug effects , Cell Membrane/metabolism , Chlortetracycline/pharmacology , Clostridium perfringens/metabolism , DNA, Bacterial/metabolism , Drug Synergism , Hydrogen-Ion Concentration , Microbial Sensitivity Tests , Microscopy, Electron, Scanning , Nisin/pharmacology , Temperature , Vancomycin/pharmacology , Virginiamycin/pharmacology , Zinc/pharmacology
12.
Ann Pharmacother ; 49(1): 69-85, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25352037

ABSTRACT

OBJECTIVE: To review the literature on the pharmacotherapy of bloodstream infections (BSI) caused by vancomycin-resistant enterococci (VRE). DATA SOURCES: A MEDLINE literature search was performed for the period 1946 to May 2014 using the search terms Enterococcus, enterococci, vancomycin-resistant, VRE, bacteremia, and bloodstream infection. References were also identified from selected review articles. STUDY SELECTION AND DATA EXTRACTION: English-language case series, cohort studies, and meta-analyses assessing the options in the pharmacotherapy of VRE BSIs in adult patients were evaluated. DATA SYNTHESIS: Studies were identified that utilized linezolid, quinupristin/dalfopristin (Q/D), and daptomycin. In all, 8 comparative retrospective cohort studies, 2 meta-analyses of daptomycin and linezolid, and 3 retrospective comparisons of linezolid and Q/D were included for review. Mortality associated with VRE BSIs was high across studies, and the ability to determine differences in outcomes between agents was confounded by the complex nature of the patients included. Two meta-analyses comparing daptomycin with linezolid for VRE BSIs found modest advantages for linezolid, but these conclusions may be hampered by heterogeneity within the included studies. CONCLUSIONS: VRE BSIs remain a difficult-to-treat clinical situation. Differences in toxicity between the agents used to treat it are clear, but therapeutic differences are more difficult to discern. Meta-analyses suggest that a moderate advantage for linezolid over daptomycin may exist, but problems with the nature of studies that they included make definitive conclusions difficult.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Gram-Positive Bacterial Infections/drug therapy , Vancomycin-Resistant Enterococci , Vancomycin/therapeutic use , Acetamides/pharmacology , Acetamides/therapeutic use , Anti-Bacterial Agents/pharmacology , Bacteremia/microbiology , Daptomycin/pharmacology , Daptomycin/therapeutic use , Gram-Positive Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/microbiology , Humans , Linezolid , Oxazolidinones/pharmacology , Oxazolidinones/therapeutic use , Vancomycin/pharmacology , Vancomycin-Resistant Enterococci/drug effects , Virginiamycin/pharmacology , Virginiamycin/therapeutic use
13.
J Appl Microbiol ; 119(6): 1515-26, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26425940

ABSTRACT

AIMS: The purpose of this study was to compare the effects of feeding virginiamycin or bacitracin methylene disalicylate (BMD), two in-feed antibiotics typically used by commercial poultry producers in the United States, on the chicken gastrointestinal microbiota. METHODS AND RESULTS: 454 pyrosequencing of the V6-V8 region of the 16S rRNA gene and quantitative PCR were employed to examine the bacterial microbiota and Clostridium perfringens, respectively, in the jejunum and caecum of market-age broiler chickens over four replicate grow-outs. CONCLUSIONS: Our results suggest that virginiamycin has a more pronounced impact on broiler gastrointestinal tract bacterial communities, relative to BMD, manifested primarily through significant enrichments in the genus Faecalibacterium in the caecum and a distinct population of Lactobacillus, OTU_02, in both the jejunum and caecum. No evidence for a difference among the diets in Cl. perfringens levels in the jejunum or caecum was observed. SIGNIFICANCE AND IMPACT OF THE STUDY: This work represents the highest resolution comparison to date of the jejunum and caecum microbiota in broilers fed either virginiamycin or BMD, and provides evidence for specific bacterial OTUs potentially involved in the health and performance benefits typically attributed to these in-feed antibiotics.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacitracin/pharmacology , Bacteria/drug effects , Gastrointestinal Microbiome/drug effects , Intestines/microbiology , Salicylates/pharmacology , Virginiamycin/pharmacology , Administration, Oral , Animals , Anti-Bacterial Agents/administration & dosage , Bacitracin/administration & dosage , Chickens , Salicylates/administration & dosage , Virginiamycin/administration & dosage
14.
Poult Sci ; 94(9): 2202-9, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26217029

ABSTRACT

An experiment was conducted to investigate the comparative effect of Scrophularia striata, Ferulago angulata, and virginiamycin (VM) on performance, intestinal microbial population, immune response, and blood constituents of broilers. A total of 300 Ross 308 male broiler chickens were randomly assigned to 5 treatments, with 5 replicates/treatment (10 chickens/pen). Birds were fed either a corn-soybean meal basal diet (control) or the basal diet supplemented with 200 mg/kg VM; 4 g/kg S. striata (SS1); 8 g/kg S. striata (SS2); 4 g/kg F. angulata (FA1); or 8 g/kg F. angulata (FA2). After 6 wk, the BW, ADG, and feed-to-gain ratio (F:G) of the VM, SS1, and FA1 groups were better (P<0.01) compared with the control group. At 42 d, cecal lactobacillus counts were higher (P=0.032) in SS2 and FA2 groups compared with the control and VM groups. In addition, broilers fed any of the diets exhibited lower coliform counts (P<0.05) in the ileum and ceca than those fed the control diet. Total and IgG antibody titers against SRBC for secondary responses, relative spleen weight, and lymphocyte counts were higher (P<0.05) in birds fed the SS2 or FA2 diet compared with the control group. Moreover, feeding the SS2 or FA2 diet decreased (P<0.05) the blood heterophil/lymphocyte ratio and plasma triglyceride level, whereas only the SS2 diet increased (P=0.037) the white blood cell counts compared with the control diet. All diets, except for the VM diet, decreased (P=0.009) the plasma cholesterol level compared to the control treatment. The plasma high-density lipoprotein cholesterol level was also increased (P=0.042) in the SS2 and FA2 groups. In conclusion, dietary S. striata or F. angulata at a level of 4 g/kg diet enhanced growth performance, which was comparable to that of VM used as an antibiotic growth promoter. Furthermore, a high dose of both herbs (8 g/kg diet) could beneficially affect the intestinal health and immune status of broilers.


Subject(s)
Anti-Bacterial Agents/pharmacology , Apiaceae/chemistry , Chickens/microbiology , Chickens/physiology , Scrophularia/chemistry , Virginiamycin/pharmacology , Animal Feed/analysis , Animal Nutritional Physiological Phenomena/drug effects , Animals , Blood Chemical Analysis/veterinary , Diet/veterinary , Dietary Supplements/analysis , Dose-Response Relationship, Drug , Immunity, Innate/drug effects , Intestines/drug effects , Intestines/microbiology , Lymphocyte Count/veterinary , Male , Random Allocation
15.
J Environ Sci Health B ; 50(11): 827-32, 2015.
Article in English | MEDLINE | ID: mdl-26357893

ABSTRACT

The multidrug resistant Enterococcus faecium (MEF) strains originating from farm animals are proliferating at a substantial pace to impact downstream food chains and could reach hospitals. This study was conducted to elucidate the drug susceptibility profile of MEF strains collected from poultry products in Ann Arbor, MI area and clinical settings from Michigan State Lab and Moffitt Cancer Center (MCC) in Florida. Presumptive positive Enterococcus isolates at species level were identified by Matrix Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) analysis. The antibiotic susceptibility profile for both poultry and clinical strains was determined by the Thermo Scientific's Sensititre conform to the National Committee for Clinical Laboratory Standards (NCCLS) and validated via quantitative real-time PCR (qPCR) methods. Out of 50 poultry samples (Turkey: n = 30; Chicken: n = 20), 36 samples were positive for Enterococcus species from which 20.83% were identified as E. faecium. All the E. faecium isolates were multidrug resistant and displayed resistance to the last alternative drug, quinupristin/dalfopristin (QD) used to treat vancomycin resistant E. faecium (VRE) in hospitals. Results indicate the presence of MEF strains in food animals and clinical settings that are also resistant to QD.


Subject(s)
Drug Resistance, Multiple, Bacterial , Enterococcus faecium/drug effects , Poultry/microbiology , Animals , Anti-Bacterial Agents/pharmacology , Chickens/microbiology , Drug Resistance , Drug Resistance, Multiple, Bacterial/genetics , Enterococcus faecium/genetics , Enterococcus faecium/isolation & purification , Hospitals , Humans , Michigan , Microbial Sensitivity Tests , Real-Time Polymerase Chain Reaction , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Turkeys/microbiology , Virginiamycin/pharmacology
16.
Antimicrob Agents Chemother ; 58(9): 5269-79, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24957822

ABSTRACT

Streptogramin antibiotics are divided into types A and B, which in combination can act synergistically. We compared the molecular interactions of the streptogramin combinations Synercid (type A, dalfopristin; type B, quinupristin) and NXL 103 (type A, flopristin; type B, linopristin) with the Escherichia coli 70S ribosome by X-ray crystallography. We further analyzed the activity of the streptogramin components individually and in combination. The streptogramin A and B components in Synercid and NXL 103 exhibit synergistic antimicrobial activity against certain pathogenic bacteria. However, in transcription-coupled translation assays, only combinations that include dalfopristin, the streptogramin A component of Synercid, show synergy. Notably, the diethylaminoethylsulfonyl group in dalfopristin reduces its activity but is the basis for synergy in transcription-coupled translation assays before its rapid hydrolysis from the depsipeptide core. Replacement of the diethylaminoethylsulfonyl group in dalfopristin by a nonhydrolyzable group may therefore be beneficial for synergy. The absence of general streptogramin synergy in transcription-coupled translation assays suggests that the synergistic antimicrobial activity of streptogramins can occur independently of the effects of streptogramin on translation.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Protein Biosynthesis/drug effects , Streptogramins/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Crystallography, X-Ray , Drug Combinations , Drug Synergism , Enterococcus faecalis/drug effects , Escherichia coli/drug effects , Haemophilus influenzae/drug effects , Microbial Sensitivity Tests , Ribosomes/drug effects , Ribosomes/ultrastructure , Staphylococcus aureus/drug effects , Streptococcus pneumoniae/drug effects , Streptogramin A/administration & dosage , Streptogramin A/pharmacology , Streptogramin A/therapeutic use , Streptogramin B/administration & dosage , Streptogramin B/pharmacology , Streptogramin B/therapeutic use , Streptogramins/administration & dosage , Streptogramins/chemistry , Streptogramins/pharmacology , Virginiamycin/administration & dosage , Virginiamycin/pharmacology , Virginiamycin/therapeutic use
17.
Int J Med Microbiol ; 304(1): 44-50, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24119565

ABSTRACT

Streptogramins are potent drugs against numerous highly resistant pathogens and therefore are used as antibiotics of last-resort human therapy. They consist of a mixture of two different types of chemical substances - the group A streptogramins, which are polyunsaturated macrolactones, and the group B streptogramins, representing cyclic hexadepsipeptides. Streptogramins are unique in their mode of action: each component alone exhibits a moderate bacteriostatic activity by binding to the bacterial 50S ribosomal subunit and thereby blocking translation, whereas the synergic combination of both substances is up to hundred fold more effective than the single compounds, resulting in a bactericidal activity. The streptogramin biosynthetic genes are organized as large antibiotic superclusters. These clusters harbour numerous regulatory genes, which encode different types of regulators that together form a complex hierarchical signalling system, which governs the regulation of streptogramin biosynthesis. Resistance is also regulated by this cascade. However, whereas resistance against streptogramins is quite well understood in diverse pathogenic organisms, only little is known about how the natural producer strains protect themselves against these toxic compounds. Here, we give an overview about the recent advances in streptogramin investigations with a main focus on the best-studied representatives, pristinamycin and virginiamycin. We concentrate on the biosynthesis of these compounds, their regulation and resistance determinants as well as their application in medicine and food industry.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biosynthetic Pathways/genetics , Drug Resistance, Bacterial , Microbial Viability/drug effects , Pristinamycin/pharmacology , Virginiamycin/pharmacology , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Drug Synergism , Food Industry , Humans , Pristinamycin/biosynthesis , Pristinamycin/chemistry , Pristinamycin/therapeutic use , Virginiamycin/biosynthesis , Virginiamycin/chemistry , Virginiamycin/therapeutic use
18.
Curr Microbiol ; 69(3): 277-85, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24748439

ABSTRACT

Bacterial contamination of fuel ethanol fermentations by lactic acid bacteria (LAB) can have crippling effects on bioethanol production. Producers have had success controlling bacterial growth through prophylactic addition of antibiotics to fermentors, yet concerns have arisen about antibiotic resistance among the LAB. Here, we report on mechanisms used by 32 LAB isolates from eight different US bioethanol facilities to persist under conditions of antibiotic stress. Minimum inhibitory concentration assays with penicillin, erythromycin, and virginiamycin revealed broad resistance to each of the antibiotics as well as high levels of resistance to individual antibiotics. Phenotypic assays revealed that antibiotic inactivation mechanisms contributed to the high levels of individual resistances among the isolates, especially to erythromycin and virginiamycin, yet none of the isolates appeared to use a ß-lactamase. Biofilm formation was noted among the majority of the isolates and may contribute to persistence under low levels of antibiotics. Nearly all of the isolates carried at least one canonical antibiotic resistance gene and many carried more than one. The erythromycin ribosomal methyltransferase (erm) gene class was found in 19 of 32 isolates, yet a number of these isolates exhibit little to no resistance to erythromycin. The erm genes were present in 15 isolates that encoded more than one antibiotic resistance mechanism, suggestive of potential genetic linkages.


Subject(s)
Bacteria/drug effects , Bacteria/metabolism , Drug Resistance, Bacterial , Ethanol/metabolism , Industrial Microbiology , Anti-Bacterial Agents/pharmacology , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Erythromycin/pharmacology , Fermentation , Genes, Bacterial , Microbial Sensitivity Tests , Molecular Sequence Data , Penicillins/pharmacology , Sequence Analysis, DNA , United States , Virginiamycin/pharmacology
19.
Biomed Environ Sci ; 27(5): 388-90, 2014 May.
Article in English | MEDLINE | ID: mdl-24827721

ABSTRACT

This study aimed to determine the in vitro activity of quinupristin-alfopristin against Streptococcus sp. isolated in China. This agent is not yet available for clinical use, but it has been tested against a high proportion of resistant Staphylococcus aureus strains. A total of 156 streptococcal isolates, which were recovered from various geographic areas and diseases, were tested using the Etest (AB Biodisk, Solna, Sweden). Quinupristin-alfopristin showed excellent activity against all of the tested streptococci isolates. These results provide useful data for the clinical use of quinupristin-alfopristin in China.


Subject(s)
Anti-Bacterial Agents/pharmacology , Streptococcus/drug effects , Virginiamycin/pharmacology , China , Microbial Sensitivity Tests
20.
Poult Sci ; 93(9): 2337-46, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25002548

ABSTRACT

The aim of this work was to test the potential use of plant-derived extracts and compounds to control Campylobacter jejuni in broiler chickens. Over a 7-wk feeding period, birds were fed a commercial diet with or without plant extracts (Acacia decurrens, Eremophila glabra), essential oil [lemon myrtle oil (LMO)], plant secondary compounds [terpinene-4-ol and α-tops (including α-terpineol, cineole, and terpinene-4-ol)], and the antibiotic virginiamycin. Traditional culture and real-time quantitative PCR techniques were used to enumerate the numbers of C. jejuni in chicken fecal and cecal samples. In addition, BW and feed intake were recorded weekly for the calculation of BW gain and feed conversion ratio. The mean log10 counts of C. jejuni were similar (P > 0.05) across treatments. However, significantly lower levels of fecal Campylobacter counts (P < 0.05) were recorded at d 41 for the α-tops treatment by culture methods. No differences (P > 0.05) in BW gain were obtained for dietary supplementation, except for the E. glabra extract, which had a negative impact (P < 0.001) on BW, resulting in sporadic death. Results from this study suggest that supplemental natural compounds used in the current study did not reduce the shedding of C. jejuni to desired levels.


Subject(s)
Campylobacter Infections/veterinary , Campylobacter jejuni/drug effects , Chickens , Dietary Supplements , Plant Extracts , Poultry Diseases/prevention & control , Virginiamycin/pharmacology , Acacia/chemistry , Animal Feed/analysis , Animals , Anti-Bacterial Agents/pharmacology , Bacterial Shedding/drug effects , Campylobacter Infections/prevention & control , Cecum/microbiology , Chickens/growth & development , Diet/veterinary , Eremophila Plant/chemistry , Feces/microbiology , Male , Poultry Diseases/microbiology , Random Allocation
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