Five New Analogs of Streptogramin Antibiotic Viridogrisein Isolated from Streptomyces niveoruber.

Five new viridogriseins B-F were isolated from Streptomyces niveoruber, along with viridogrisein and griseoviridin which belong to streptogramin family antibiotics. A combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and the advanced Marfey's method elucidated the structures of viridogriseins B-F, each featuring distinct constituent amino acids. Consistent with other streptogramin family antibiotics, these viridogrisein analogs exhibited potent antibacterial activity against Staphylococcus aureus. Furthermore, equimolar mixtures of each viridogrisein analog and griseoviridin inhibited the growth of S. aureus more potently than each analog treatment alone. Finally, an in vitro functional analysis of SgvY, encoded in the viridogrisein biosynthetic gene cluster, revealed that SgvY detoxifies viridogrisein against S. aureus by linearization. Considering that viridogrisein is not autotoxic to S. niveoruber, SgvY likely contributes to the self-resistance system against viridogrisein in S. niveoruber.

The antimicrobial activity of cethromycin against Staphylococcus aureus and compared with erythromycin and telithromycin.

BACKGROUND: This study aims to explore the antibacterial activity of cethromycin against Staphylococcus aureus (S. aureus), and its relationship with multilocus sequence typing (MLST), erythromycin ribosomal methylase (erm) genes and macrolide-lincosamide-streptogramin B (MLSB) phenotypes of S. aureus. RESULTS: The minimum inhibitory concentrations (MICs) of cethromycin against 245 S. aureus clinical isolates ranged from 0.03125 to ≥ 8 mg/L, with the resistance of 38.8% in 121 methicillin-resistant S. aureus (MRSA). This study also found that cethromycin had strong antibacterial activity against S. aureus, with the MIC ≤ 0.5 mg/L in 55.4% of MRSA and 60.5% of methicillin-sensitive S. aureus (MSSA), respectively. The main MLSTs of 121 MRSA were ST239 and ST59, and the resistance of ST239 isolates to cethromycin was higher than that in ST59 isolates (P = 0.034). The top five MLSTs of 124 MSSA were ST7, ST59, ST398, ST88 and ST120, but there was no difference in the resistance of MSSA to cethromycin between these STs. The resistance of ermA isolates to cethromycin was higher than that of ermB or ermC isolates in MRSA (P = 0.016 and 0.041, respectively), but the resistance of ermB or ermC isolates to cethromycin was higher than that of ermA isolates in MSSA (P = 0.019 and 0.026, respectively). The resistance of constitutive MLSB (cMLSB) phenotype isolates to cethromycin was higher than that of inducible MLSB (iMLSB) phenotype isolates in MRSA (P < 0.001) or MSSA (P = 0.036). The ermA, ermB and ermC genes was mainly found in ST239, ST59 and ST1 isolates in MRSA, respectively. Among the MSSA, the ermC gene was more detected in ST7, ST88 and ST120 isolates, but more ermB genes were detected in ST59 and ST398 isolates. The cMLSB phenotype was more common in ST239 and ST59 isolates of MRSA, and was more frequently detected in ST59, ST398, and ST120 isolates of MSSA. CONCLUSION: Cethromycin had strong antibacterial activity against S. aureus. The resistance of MRSA to cethromycin may had some clonal aggregation in ST239. The resistance of S. aureus carrying various erm genes or MLSB phenotypes to cethromycin was different.

Strategies of virginiamycin supplementation in the postweaning phase on growth performance and carcass quality of beef cattle.

The present study evaluated the effects of supplementing VM in grazing cattle during the rearing phase on performance and carcass quality of beef cattle in the finishing phase. Two experiments with a randomized block design were conducted in consecutive years to contrast two post-weaning supplementation strategies using VM at 45 mg/100 kg body weight (BW). In the first year, treatments were protein supplement in the dry season and mineral supplement in the rainy season versus the addition of VM both in the protein and mineral supplements. In the second year, was contrasted with protein supplement in the dry season and protein-energy supplement in the rainy season. Performance, carcass traits, and carcass quality were evaluated at the end of both phases. In Year 1, adding VM in mineral supplement increased final backfat thickness (P=0.05), backfat gain (P=0.06), final rump fat thickness (P=0.02), and rump fat gain (P=0.01). In the finishing phase, VM-treated cattle had a greater dry matter intake (P=0.03) and tended to show a greater backfat thickness than non-treated cattle (P=0.07). In Year 2, no VM effects were observed on post-weaning phase performance and carcass traits. However, cattle-fed VM during the post-weaning phase tended to show a lower feed conversion ratio (P=0.09) and had a significantly higher gross feed efficiency (P=0.03) than non-treated cattle at slaughter. Virginiamycin supplementation during rearing on pasture improves performance and carcass fattening in the growth phase and has a residual effect in the finishing phase that may reflect greater backfat thickness and gross feed efficiency.

NMR characterization of streptogramin B and L-156,587, a non-synergistic pair of the streptogramin family antibiotic complexes produced inductively by a combined culture of Streptomyces albogriseolus and Tsukamurella pulmonis.

The complete 1 H and 13 C NMR characterization of streptogramin B (1), the major component of a clinically important synergistic antibiotic complex, was presented for the first time, along with those of L-156,587 (2), a dehydrated congener of streptogramin A (3). Compounds 1 and 2 were not synergistic and produced by Streptomyces albogriseolus in co-culture with Tsukamurella pulmonis, which poses a question on the adaptive significance of the induced production of this antibiotic pair.

Genomic Insights of First ermB-Positive ST338-SCCmecVT/CC59 Taiwan Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus in Poland.

We report the first Polish representative of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), lukS/F-PV-positive, encoding the ermB gene, as a genetic determinant of constitutive resistance to macrolides, lincosamides, and streptogramin B antibiotics, cMLS-B. This is the first detection of the CA-MRSA strain responsible for nosocomial infection in the Warsaw Clinical Hospital. Resistance to ß-lactams associates with a composite genetic element, SCCmec cassette type VT (5C2&5). We assigned the strain to sequence type ST338 (single-locus variant of ST59), clonal complex CC59, spa-type t437, and agr-type I. Genomic-based comparison was designated SO574/12 as an international Taiwan clone, which has been so far described mainly in the Asia-Pacific region. The ermB gene locates on the chromosome within the 14,690 bp mobile element structure, i.e., the MESPM1-like structure, which also encodes aminoglycoside- and streptothricin-resistance genes. The MESPM1-like structure is a composite transposon containing Tn551, flanked by direct repeats of IS1216V insertion sequences, which probably originates from Enterococcus. The ermB is preceded by the 273 bp regulatory region that contains the regulatory 84 bp ermBL ORF, encoding the 27 amino acid leader peptides. The latest research suggests that a new leader peptide, ermBL2, also exists in the ermB regulatory region. Therefore, the detailed function of ermBL2 requires further investigations.

Staphylococcus aureus with an erm-mediated constitutive macrolide-lincosamide-streptogramin B resistance phenotype has reduced susceptibility to the new ketolide, solithromycin.

BACKGROUND: Solithromycin, the fourth generation of ketolides, has been demonstrated potent antibacterial effect against commonly-isolated gram-positive strains. However, Staphylococcus aureus (S. aureus) strains with a higher solithromycin MIC have already been emerged, the mechanism of which is unknown. METHODS: Antimicrobial susceptibility test was performed on 266 strains of S. aureus. The antibiotic resistance phenotype of erm-positive strain was determined by D-zone test. Spontaneous mutation frequency analysis was performed to compare the risk levels for solithromycin resistance among different strains. Efflux pumps and mutational analysis of ribosomal fragments as well as erm(B) gene domains were detected. Quantitative reverse transcription polymerase chain reaction was conducted to compare the transcriptional expression of the erm gene between the constitutive macrolide-lincosamide-streptogramin B (cMLSB)- and inducible MLSB (iMLSB)-phenotypes. RESULTS: In the erm-positive S. aureus strains, the minimum inhibitory concentration (MIC)50/90 of solithromycin (2/> 16 mg/L) was significantly higher than that in the erm-negative strains (0.125/0.25 mg/L). Of note, the MIC50 value of the strains with iMLSB (0.25 mg/L) was significantly lower than that of the strains with cMLSB (4 mg/L). A comparison among strains demonstrated that the median mutational frequency in isolates with cMLSB (> 1.2 × 10- 4) was approximately > 57-fold and > 3333-fold higher than that in iMLSB strains (2.1 × 10- 6) and in erythromycin-sensitive strains (3.6 × 10- 8), respectively. The differential antibiotic in vitro activity against strains between cMLSB and iMLSB could not be explained by efflux pump carriers or genetic mutations in the test genes. The expression of the erm genes in strains with cMLSB did not differ from that in strains with iMLSB. CONCLUSIONS: The reduced susceptibility to solithromycin by S. aureus was associated with the cMLSB resistance phenotype mediated by erm.

Azithromycin Pharmacodynamics against Persistent Haemophilus influenzae in Chronic Obstructive Pulmonary Disease.

The pharmacodynamic profile of azithromycin against persistent strains of nontypeable Haemophilus influenzae (NTHi) from chronic obstructive pulmonary disease (COPD) patients was characterized. Azithromycin displayed differential concentration-dependent activities (R2 ≥ 0.988); the pharmacodynamic response was attenuated when we compared the "first" and "last" strains of NTHi that persisted in the airways of the same patient for 819 days (the 50% effective concentration [EC50] increased more than 50 times [0.0821 mg/liter versus 4.23 mg/liter]). In the hollow-fiber infection model, NTHi viability was maintained throughout simulated azithromycin (Zithromax) Z-Pak regimens over 10 days.

Assessment of the In Vivo Activity of SPR741 in Combination with Azithromycin against Multidrug-Resistant Enterobacteriaceae Isolates in the Neutropenic Murine Thigh Infection Model.

SPR741 is a novel agent with structural similarity to polymyxins that is capable of potentiating the activities of various classes of antibiotics. Previously published studies indicated that although Enterobacteriaceae isolates had minimal susceptibilities to azithromycin (AZM), the in vitro antimicrobial activity of AZM against Enterobacteriaceae was enhanced when it was combined with SPR741. The current study evaluated the in vivo activity of human-simulated regimens (HSR) of AZM equivalent to clinical doses of 500 mg given intravenously (i.v.) every 24 h (q24h) and SPR741 equivalent to clinical doses of 400 mg q8h i.v. (1-h infusion), alone and in combination, against multidrug-resistant (MDR) Enterobacteriaceae We studied 30 MDR Enterobacteriaceae isolates expressing a wide spectrum of ß-lactamases (ESBL, NDM, VIM, and KPC), including a subset of isolates positive for genes conferring macrolide resistance (mphA, mphE, ermB, and msr). In vivo activity was assessed as the change in log10 CFU per thigh at 24 h compared with 0 h. Treatment with AZM alone was associated with net growth of 2.60 ± 0.83 log10 CFU/thigh. Among isolates with AZM MICs of ≤16 mg/liter, treatment with AZM-SPR741was associated with an average reduction in bacterial burden of -0.53 ± 0.82 log10 CFU/thigh, and stasis to 1-log kill was observed in 9/11 isolates (81.8%). Combination therapy with an AZM-SPR741 HSR showed promising in vivo activity against MDR Enterobacteriaceae isolates with AZM MICs of ≤16 mg/liter, including those producing a variety of ß-lactamases. These data support a potential role for AZM-SPR741 in the treatment of infections due to MDR Enterobacteriaceae.

Nasal colonisation, antimicrobial susceptibility and genotypic pattern of Staphylococcus aureus among agricultural biotechnology students in Besut, Terengganu, east coast of Malaysia.

BACKGROUND: This study aimed to profile the antimicrobial susceptibility and presence of resistance and virulence genes of methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA nasal carriage, by means of genotypic analyses, in students of a tertiary institution in the state of Terengganu, east coast of Malaysia. METHODS: A total of 370 agricultural biotechnology students from Universiti Sultan Zainal Abidin in Besut, Terengganu, were enrolled in this study. Antimicrobial susceptibility profiles were evaluated by standard methods. PCR detection of resistance and virulence genes was performed on S. aureus that were methicillin-resistant, macrolide-lincosamide-streptogramin B (MLSB )-positive phenotype and/or positive for the leukocidin (pvl) gene followed by staphylococcal cassette chromosome mec (SCCmec), staphylococcal protein A (spa) and accessory gene regulator (agr) typing. RESULTS: One hundred and nineteen of 370 students carried S. aureus (32%); 18 of the isolates were MRSA (15%). Erythromycin resistance was detected in 20% (24/119) of which 15% (18/119) were MRSA and 5% (6/119) MSSA. Among the 24 erythromycin-resistant isolates, D-test was positive in 29% (7/24) displaying inducible MLSB , whereas the remaining 71% (17/24) showed constitutive MLSB phenotypes. Nine (7.6%) of 119 isolates were pvl positive: 44% MRSA (4/9) and 56% MSSA (5/9). Staphylococcal surface protein sasX gene was present in 92% of MRSA and 8% of MSSA isolates. The majority of MRSA isolates were agr type I (15/18; 83%). Five spa types identified with spa t037 were predominant, followed by spa types (t304 and t8696) as newly reported Malaysian MRSA in a community setting. CONCLUSION: The presence of MRSA with SCCmec of hospital-associated features and globally recognised spa types in community setting is worrisome. Furthermore, the presence of MLSB strains among multidrug-resistant (MDR) S. aureus with sasX as well as pvl-positive isolates highlights the potential risk of a community setting in facilitating the dissemination of both virulence and resistance determinants.

A Novel erm(44) Gene Variant from a Human Staphylococcus saprophyticus Isolate Confers Resistance to Macrolides and Lincosamides but Not Streptogramins.

A novel erm(44) gene variant, erm(44)v, has been identified by whole-genome sequencing in a Staphylococcus saprophyticus isolate from the skin of a healthy person. It has the particularity to confer resistance to macrolides and lincosamides but not to streptogramin B when expressed in S. aureus The erm(44)v gene resides on a 19,400-bp genomic island which contains phage-associated proteins and is integrated into the chromosome of S. saprophyticus.

New Macrolide-Lincosamide-Streptogramin B Resistance Gene erm(48) on the Novel Plasmid pJW2311 in Staphylococcus xylosus.

Whole-genome sequencing of Staphylococcus xylosus strain JW2311 from bovine mastitis milk identified the novel 49.3-kb macrolide-lincosamide-streptogramin B (MLSB) resistance plasmid pJW2311. It contained the macrolide resistance gene mph(C), the macrolide-streptogramin B resistance gene msr(A), and the new MLSB resistance gene erm(48) and could be transformed into Staphylococcus aureus by electroporation. Functionality of erm(48) was demonstrated by cloning and expression in S. aureus.

Identification and utilization of two important transporters: SgvT1 and SgvT2, for griseoviridin and viridogrisein biosynthesis in Streptomyces griseoviridis.

BACKGROUND: Griseoviridin (GV) and viridogrisein (VG, also referred as etamycin), both biosynthesized by a distinct 105 kb biosynthetic gene cluster (BGC) in Streptomyces griseoviridis NRRL 2427, are a pair of synergistic streptogramin antibiotics and very important in treating infections of many multi-drug resistant microorganisms. Three transporter genes, sgvT1-T3 have been discovered within the 105 kb GV/VG BGC, but the function of these efflux transporters have not been identified. RESULTS: In the present study, we have identified the different roles of these three transporters, SgvT1, SgvT2 and SgvT3. SgvT1 is a major facilitator superfamily (MFS) transporter whereas SgvT2 appears to serve as the sole ATP-binding cassette (ABC) transporter within the GV/VG BGC. Both proteins are necessary for efficient GV/VG biosynthesis although SgvT1 plays an especially critical role by averting undesired intracellular GV/VG accumulation during biosynthesis. SgvT3 is an alternative MFS-based transporter that appears to serve as a compensatory transporter in GV/VG biosynthesis. We also have identified the γ-butyrolactone (GBL) signaling pathway as a central regulator of sgvT1-T3 expression. Above all, overexpression of sgvT1 and sgvT2 enhances transmembrane transport leading to steady production of GV/VG in titers ≈ 3-fold greater than seen for the wild-type producer and without any notable disturbances to GV/VG biosynthetic gene expression or antibiotic control. CONCLUSIONS: Our results shows that SgvT1-T2 are essential and useful in GV/VG biosynthesis and our effort highlight a new and effective strategy by which to better exploit streptogramin-based natural products of which GV and VG are prime examples with clinical potential.

Drug sensitivity pattern of various Staphylococcus species isolated at a tertiary care hospital.

BACKGROUND: Staphylococcus aureus and other Staphylococcus species are important pathogenic organisms and are responsible for various hospital infections. These are the predominant organisms found in pus and blood culture isolates. Infections arising due to these bacterial isolates are difficult to treat because of developing multidrug resistance. METHODS: Over a 1-year period at a tertiary care hospital laboratory, 524 Staphylococci species were isolated from pus, blood and urine samples and species-level identification was done. RESULTS: S. aureus formed the predominant species (70.8%) followed by coagulase-negative Staphylococcus (CoNS) (29.20%). S. aureus (91%) was the main isolate from pus samples; however, CoNS was isolated in equally higher proportion in blood culture (63.58%). Among the CoNS, Staphylococcus hemolyticus was the main isolate (9.3%). ß-Lactamase production, alteration of PBP and MLSB resistance were seen in variable degrees in different species. CONCLUSION: CoNS group of Staphylococci is becoming an important cause of infection at tertiary care centres. The increased multidrug resistance among various Staphylococcus species is a cause of great concern and requires adequate measures to prevent the spread of these microorganisms in the hospital and the community.

Pristinamycin: old drug, new tricks?

Osteoarticular infections with Gram positive bacteria present an increasing challenge in an era of multidrug-resistant organisms. Prolonged intravenous antibiotic treatment is often required, with associated risks, costs and difficulties with administration; a safe, effective oral option would be ideal for this indication. Pristinamycin, an oral streptogramin antibiotic with bactericidal activity against Gram positive organisms including methicillin-resistant Staphylococcus aureus, has been used for over 50 years in Europe for the treatment of osteoarticular infections. We review the published evidence for the treatment of native bone and prosthesis-related osteoarticular infections with pristinamycin.

Streptogramins - two are better than one!

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.

Cross-reactivity among and between macrolides, lincosamides, and streptogramins: Study on the French pharmacovigilance database.

BACKGROUND: Hypersensitivity reactions (HSR) are reported for the macrolides, lincosamides, and streptogramins (MLS) antibiotic family. Data about cross-reactivity among and between MLS remain scarce or controversial. OBJECTIVES: The aim of this study was to provide an overview of hypersensitivity cross-reactions among MLSs based on data extracted from the French National Pharmacovigilance Database (FPVD). METHODS: Cases of HSR to MLSs reported between January 1985 and December 2019 were extracted from the FPVD using standardized MedDRA queries (SMQ). Cases including an allergological test involving multiple MLSs and giving at least one positive result were included. RESULTS: Of the 8394 cases reviewed, 149 were included. HSR mainly involved pristinamycin (n = 83; 53.2%) and spiramycin (n = 31; 19.9%). HSR to MLS was immediate in 54 cases and delayed in 94 cases. Skin tests represented the majority of the allergological tests performed (n = 728; 84.7%), followed by reintroduction tests (n = 79; 9.2%). Eighty-six cross-reactivities among MLS were identified in 62 cases (41.6%). All the 25 explorations performed for streptogramins showed cross-reactivities, but only 30/253 among macrolides (11.9%). Cross-reactivities between the three MLS were observed in 31/322 (9.6%) of the allergological explorations. CONCLUSION: This study highlights the possibility of cross-reactivity among and between MLSs. Dermatologists and allergologists managing patients with HSR to MLSs should be aware of a risk of cross-reactivity among the macrolides and between the different classes of MLS and to perform MLSs allergological testing before recommending an alternative antibiotic, especially in severe drug hypersensitivity from the MLS family.

Draft genome sequence data of the multidrug-resistant bacterium Staphylococcus haemolyticus 010503B isolated from an aerosol sample in a hospital waiting area in Thailand.

Staphylococcus haemolyticus 010503B is a multidrug-resistant bacterium isolated from an outpatient clinic in a hospital waiting area in Thailand. Here we present the draft genome sequence of S. haemolyticus 010503B. The paired-end reads were generated on the Illumina NextSeq 550 sequencer using genomic DNA from the pure culture of S. haemolyticus 010503B. The draft genome consisted of 114 contigs with a total size of 2,457,654 base pairs, an N50 of 57,312 base pairs and a GC content of 32.60%. The dDDH between 010503B and Staphylococcus haemolyticus SM 131T was 91.9%, identifying the strain as Staphylococcus haemolyticus. The data presented holds promise for bacterial classification, comparative genomics, analysing antimicrobial resistance comprehensively, and assessing bacterial virulence factors of S. haemolyticus. The draft genome sequence data has been deposited at NCBI under Bioproject accession number PRJNA550309.

Macrolide and lincosamide resistance of Streptococcus agalactiae in pregnant women in Poland.

Knowing about the antibiotic resistance, serotypes, and virulence-associated genes of Group B Streptococcus for epidemiological and vaccine development is very important. We have determined antimicrobial susceptibility patterns, serotype, and virulence profiles. The antibiotic susceptibility was assessed for a total of 421 Streptococcus agalactiae strains, isolated from pregnant women and neonates. Then, 89 erythromycin and/or clindamycin-resistant strains (82 isolates obtained from pregnant women and seven isolates derived from neonates) were assessed in detail. PCR techniques were used to identify the studied strains, perform serotyping, and assess genes encoding selected virulence factors. Phenotypic and genotypic methods determined the mechanisms of resistance. All tested strains were sensitive to penicillin and levofloxacin. The constitutive MLSB mechanism (78.2%), inducible MLSB mechanism (14.9%), and M phenotype (6.9%) were identified in the macrolide-resistant strains. It was found that macrolide resistance is strongly associated with the presence of the ermB gene and serotype V. FbsA, fbsB, fbsC, scpB, and lmb formed the most recurring pattern of genes among the nine surface proteins whose genes were analysed. A minority (7.9%) of the GBS isolates exhibited resistance to lincosamides and macrolides, or either, including those that comprised the hypervirulent clone ST-17. The representative antibiotic resistance pattern consisted of erythromycin, clindamycin, and tetracycline resistance (71.9%). An increase in the fraction of strains resistant to macrolides and lincosamides indicates the need for monitoring both the susceptibility of these strains and the presence of the ST-17 clone.

pDB2011, a 7.6 kb multidrug resistance plasmid from Listeria innocua replicating in Gram-positive and Gram-negative hosts.

pDB2011, a multidrug resistance plasmid isolated from the foodborne Listeria innocua strain TTS-2011 was sequenced and characterized. Sequence analysis revealed that pDB2011 had a length of 7641 bp and contained seven coding DNA sequences of which two were annotated as replication proteins, one as a recombination/mobilization protein and one as a transposase. Furthermore, pDB2011 harbored the trimethoprim, spectinomycin and macrolide-lincosamide-streptogramin B resistance genes dfrD, spc and erm(A), respectively. However, pDB2011 was only associated with trimethoprim and spectinomycin resistance phenotypes and not with phenotypic resistance to erythromycin. A region of the plasmid encoding the resistance genes spc and erm(A) plus the transposase was highly similar to Staphylococcus aureus transposon Tn554. The dfrD gene was 100% identical to dfrD found in a number of Listeria monocytogenes isolates. Additionally, assessment of the potential host range of pDB2011 revealed that the plasmid was able to replicate in Lactococcus lactis subsp. cremoris MG1363 as well as in Escherichia coli MC1061 and DH5α. This study reports the first multidrug resistance plasmid in L. innocua. A large potential for dissemination of pDB2011 is indicated by its host range of both Gram-positive and Gram-negative bacteria.

Regio-selectively reduced streptogramin A analogue, 5,6-dihydrovirginiamycin M1 exhibits improved potency against MRSA.

A newly reduced macrocyclic lactone antibiotic streptogramin A, 5,6-dihydrovirginiamycin M1 was created by feeding virginiamycin M1 into a culture of recombinant Streptomyces venezuelae. Its chemical structure was spectroscopically elucidated, and this streptogramin A analogue showed twofold higher antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) compared with its parent molecule virginiamycin M1. Docking studies using the model of streptogramin A acetyltransferase (VatA) suggested that the newly generated analogue binds tighter with overall lower free energy compared with the parent molecule virginiamycin M1. This hypothesis was validated experimentally through the improvement of efficacy of the new analogue against MRSA strains. The biotransformation approach presented herein could have a broad application in the production of reduced macrocyclic molecules.