scholarly journals In VitroActivity against Staphylococcus aureus of a Novel Antimicrobial Agent, PRF-119, a Recombinant Chimeric Bacteriophage Endolysin

2011 ◽  
Vol 55 (9) ◽  
pp. 4416-4419 ◽  
Author(s):  
Evgeny A. Idelevich ◽  
Christof von Eiff ◽  
Alexander W. Friedrich ◽  
Domenico Iannelli ◽  
Guoqing Xia ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agent ◽  
The Novel ◽  
Good Activity ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Content Type ◽  
Microdilution Method ◽  
Antistaphylococcal Activity ◽  
Bacteriophage Endolysin

ABSTRACTAntistaphylococcal activity of the novel chimeric endolysin PRF-119 was evaluated with the microdilution method. The MIC50and MIC90of 398 methicillin-susceptibleStaphylococcus aureusisolates were 0.098 μg/ml and 0.391 μg/ml, respectively (range, 0.024 to 0.780 μg/ml). Both the MIC50and MIC90values of 776 methicillin-resistantS. aureusisolates were 0.391 μg/ml (range, 0.024 to 1.563 μg/ml). All 192 clinical isolates of coagulase-negative staphylococci exhibited MIC values of >50 μg/ml. In conclusion, PRF-119 exhibited very good activity specifically againstS. aureus.

scholarly journals In Vitro Activities of Noveltrans-3,5-Disubstituted Pyrrolidinylthio-1β-Methylcarbapenems with Potent Activities against Methicillin-Resistant Staphylococcus aureus andPseudomonas aeruginosa

2000 ◽  
Vol 44 (3) ◽  
pp. 489-495 ◽  
Author(s):  
Rie Nagano ◽  
Kaneyoshi Shibata ◽  
Yuka Adachi ◽  
Hideaki Imamura ◽  
Terutaka Hashizume ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Side Chain ◽  
The Novel ◽  
Good Activity ◽  
Penicillin Binding Protein ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
The Family

ABSTRACT The in vitro activities of the novel 1β-methylcarbapenems J-111,225, J-114,870, and J-114,871, which have a structurally unique side chain that consists of a trans-3,5-disubstituted 5-arylpyrrolidin-3-ylthio moiety at the C-2 position, were compared with those of reference antibiotics. Among isolates of both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS), 90% were inhibited by J-111,347 (prototype), J-111,225, J-114,870, and J-114,871 at concentrations of 2, 4, 4, and 4 μg/ml (MICs at which 90% of isolates are inhibited [MIC90s]), respectively, indicating that these agents were 32- to 64-fold more potent than imipenem, which has an MIC90 of 128 μg/ml. Although these drugs were less active in vitro than vancomycin, which had MIC90s of 1 and 2 μg/ml for MRSA and MRCoNS, respectively, the new carbapenems displayed better killing kinetics than vancomycin. The potent anti-MRSA activity was ascribed to the excellent affinities of the new carbapenems for penicillin-binding protein 2a of MRSA. Since the new carbapenems also exhibited good activity against gram-positive and -negative bacteria including clinically important pathogens such as penicillin-resistantStreptococcus pneumoniae, Haemophilus influenzae, members of the family Enterobacteriaceae,Pseudomonas aeruginosa, and Clostridium difficile, as well as MRSA, the novel carbapenems are worthy of further evaluation.

scholarly journals In VitroActivity of Retapamulin against Staphylococcus aureus Resistant to Various Antimicrobial Agents

2013 ◽  
Vol 57 (9) ◽  
pp. 4547-4550 ◽  
Author(s):  
Louis D. Saravolatz ◽  
Joan Pawlak ◽  
Stephanie N. Saravolatz ◽  
Leonard B. Johnson
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Good Activity ◽  
Methicillin Resistant ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Time Kill

ABSTRACTRetapamulin and six other antimicrobial agents were evaluated against 155 methicillin-resistantStaphylococcus aureus(MRSA) isolates, including strains resistant to vancomycin, linezolid, daptomycin, and mupirocin by microdilution tests. Time-kill assays were performed against representative MRSA, vancomycin-intermediateS. aureus(VISA), and vancomycin-resistantS. aureus(VRSA) isolates. Retapamulin and mupirocin demonstrated MIC90s of 0.12 μg/ml and 8 μg/ml, respectively, with resistance seen in 2.6% and 10% of isolates, respectively. Retapamulin maintained good activity against 94% (15/16) of mupirocin-resistant isolates.

scholarly journals Characterization of Methicillin-Resistant Staphylococcus aureus Isolates from Food and Food Products of Poultry Origin in Germany

2011 ◽  
Vol 77 (20) ◽  
pp. 7151-7157 ◽  
Author(s):  
Andrea T. Feßler ◽  
Kristina Kadlec ◽  
Melanie Hassel ◽  
Tomasz Hauschild ◽  
Christopher Eidam ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Meat Products ◽  
Poultry Meat ◽  
The Novel ◽  
Methicillin Resistant ◽  
Content Type ◽  
Turkey Meat ◽  
Poultry Products ◽  
Type Iv ◽  
Toxic Shock Syndrome Toxin

ABSTRACTDuring a survey of fresh chicken and turkey meat as well as chicken and turkey meat products for the presence of methicillin-resistantStaphylococcus aureus(MRSA) isolates in Germany, 32 (37.2%) of 86 samples were MRSA positive. Twenty-eight of these MRSA isolates belonged to clonal complex 398 (CC398), which is widespread among food-producing animals. These CC398 isolates carried SCCmecelements of type IV or V and exhibitedspatype t011, t034, t899, t2346 or t6574 and either the knowndrutypes dt2b, dt6j, dt10a, dt10q, dt11a, dt11v, and dt11ab or the noveldrutypes dt6m, dt10as, and dt10at. In addition, two MRSA sequence type 9 (ST9) isolates with a type IV SCCmeccassette,spatype t1430, anddrutype dt10a as well as single MRSA ST5 and ST1791 isolates with a type III SCCmeccassette,spatype t002, anddrutype dt9v were identified. All but two isolates were classified as multiresistant. A wide variety of resistance phenotypes and genotypes were detected. All isolates were negative for the major virulence factors, such as Panton-Valentine leukocidin, toxic shock syndrome toxin 1, or exfoliative toxins. In contrast to the MRSA CC398 isolates, the four ST9, ST5, or ST1791 isolates harbored theegcgene cluster for enterotoxin G, I, M, N, O, and U genes. Although the relevance of contamination of fresh poultry meat or poultry products with MRSA is currently unclear, the presence of multiresistant and, in part, enterotoxigenic MRSA emphasizes the need for further studies to elucidate possible health hazards for consumers.

scholarly journals Identification of Pyruvate Kinase in Methicillin-Resistant Staphylococcus aureus as a Novel Antimicrobial Drug Target

2011 ◽  
Vol 55 (5) ◽  
pp. 2042-2053 ◽  
Author(s):  
Roya Zoraghi ◽  
Raymond H. See ◽  
Peter Axerio-Cilies ◽  
Nag S. Kumar ◽  
Huansheng Gong ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pyruvate Kinase ◽  
Drug Target ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibacterial Drug ◽  
Methicillin Resistant ◽  
Content Type ◽  
Antistaphylococcal Activity

ABSTRACTNovel classes of antimicrobials are needed to address the challenge of multidrug-resistant bacteria such as methicillin-resistantStaphylococcus aureus(MRSA). Using the architecture of the MRSA interactome, we identified pyruvate kinase (PK) as a potential novel drug target based upon it being a highly connected, essential hub in the MRSA interactome. Structural modeling, including X-ray crystallography, revealed discrete features of PK in MRSA, which appeared suitable for the selective targeting of the bacterial enzyme.In silicolibrary screening combined with functional enzymatic assays identified an acyl hydrazone-based compound (IS-130) as a potent MRSA PK inhibitor (50% inhibitory concentration [IC50] of 0.1 μM) with >1,000-fold selectivity over human PK isoforms. Medicinal chemistry around the IS-130 scaffold identified analogs that more potently and selectively inhibited MRSA PK enzymatic activity andS. aureusgrowthin vitro(MIC of 1 to 5 μg/ml). These novel anti-PK compounds were found to possess antistaphylococcal activity, including both MRSA and multidrug-resistantS. aureus(MDRSA) strains. These compounds also exhibited exceptional antibacterial activities against other Gram-positive genera, including enterococci and streptococci. PK lead compounds were found to be noncompetitive inhibitors and were bactericidal. In addition, mutants with significant increases in MICs were not isolated after 25 bacterial passages in culture, indicating that resistance may be slow to emerge. These findings validate the principles of network science as a powerful approach to identify novel antibacterial drug targets. They also provide a proof of principle, based upon PK in MRSA, for a research platform aimed at discovering and optimizing selective inhibitors of novel bacterial targets where human orthologs exist, as leads for anti-infective drug development.

scholarly journals Dissemination of the Samecfr-Carrying Plasmid among Methicillin-Resistant Staphylococcus aureus and Coagulase-Negative Staphylococcal Isolates in China

2015 ◽  
Vol 59 (6) ◽  
pp. 3669-3671 ◽  
Author(s):  
Jia Chang Cai ◽  
Yan Yan Hu ◽  
Hong Wei Zhou ◽  
Gong-Xiang Chen ◽  
Rong Zhang
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Mobile Element ◽  
Sequence Type ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Content Type ◽  
Staphylococcal Species ◽  
Complete Sequencing ◽  
Staphylococcal Cassette Chromosome

ABSTRACTSixcfr-harboring methicillin-resistantStaphylococcus aureus(MRSA) isolates, which belonged to the same clone of sequence type 5 (ST5)-staphylococcal cassette chromosomemecelement II (SCCmecII)-spat311, were investigated in this study. Complete sequencing of acfr-carrying plasmid, pLRSA417, revealed an 8,487-bp fragment containing a Tn4001-like transposon,cfr,orf1, and ISEnfa4. This segment, first identified in an animal plasmid, pSS-01, was observed in several plasmids from clinical coagulase-negative staphylococci in China, suggesting that thecfrgene, which might originate from livestock, was located in the same mobile element and disseminated among different clinical staphylococcal species.

scholarly journals Characterization of a Novel Arginine Catabolic Mobile Element (ACME) and Staphylococcal Chromosomal CassettemecComposite Island with Significant Homology to Staphylococcus epidermidis ACME Type II in Methicillin-Resistant Staphylococcus aureus Genotype ST22-MRSA-IV

2011 ◽  
Vol 55 (5) ◽  
pp. 1896-1905 ◽  
Author(s):  
Anna C. Shore ◽  
Angela S. Rossney ◽  
Orla M. Brennan ◽  
Peter M. Kinnevey ◽  
Hilary Humphreys ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Mobile Element ◽  
Type I ◽  
Type Ii ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Content Type ◽  
Arginine Catabolic Mobile Element

ABSTRACTThe arginine catabolic mobile element (ACME) is prevalent among methicillin-resistantStaphylococcus aureus(MRSA) isolates of sequence type 8 (ST8) and staphylococcal chromosomal cassettemec(SCCmec) type IVa (USA300) (ST8-MRSA-IVa isolates), and evidence suggests that ACME enhances the ability of ST8-MRSA-IVa to grow and survive on its host. ACME has been identified in a small number of isolates belonging to other MRSA clones but is widespread among coagulase-negative staphylococci (CoNS). This study reports the first description of ACME in two distinct strains of the pandemic ST22-MRSA-IV clone. A total of 238 MRSA isolates recovered in Ireland between 1971 and 2008 were investigated for ACME using a DNA microarray. Twenty-three isolates (9.7%) were ACME positive, and all were either MRSA genotype ST8-MRSA-IVa (7/23, 30%) or MRSA genotype ST22-MRSA-IV (16/23, 70%). Whole-genome sequencing and comprehensive molecular characterization revealed the presence of a novel 46-kb ACME and staphylococcal chromosomal cassettemec(SCCmec) composite island (ACME/SCCmec-CI) in ST22-MRSA-IVh isolates (n= 15). This ACME/SCCmec-CI consists of a 12-kb DNA region previously identified in ACME type II inS. epidermidisATCC 12228, a truncated copy of the J1 region of SCCmectype I, and a complete SCCmectype IVh element. The composite island has a novel genetic organization, with ACME located withinorfXand SCCmeclocated downstream of ACME. One PVL locus-positive ST22-MRSA-IVa isolate carried ACME located downstream of SCCmectype IVa, as previously described in ST8-MRSA-IVa. These results suggest that ACME has been acquired by ST22-MRSA-IV on two independent occasions. At least one of these instances may have involved horizontal transfer and recombination events between MRSA and CoNS. The presence of ACME may enhance dissemination of ST22-MRSA-IV, an already successful MRSA clone.

scholarly journals A Clonal Complex 12 Methicillin-Resistant Staphylococcus aureus Strain, West Australian MRSA-59, Harbors a Novel Pseudo-SCCmecElement

2015 ◽  
Vol 59 (11) ◽  
pp. 7142-7144 ◽  
Author(s):  
Stefan Monecke ◽  
Geoffrey W. Coombs ◽  
Julie Pearson ◽  
Helmut Hotzel ◽  
Peter Slickers ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Clonal Complex ◽  
Copper Resistance ◽  
Aureus Strain ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Content Type ◽  
Reading Frame ◽  
Link Type

ABSTRACTA West Australian methicillin-resistantStaphylococcus aureusstrain (WA MRSA-59) was characterized by microarray and sequencing. Its pseudo-staphylococcal cassette chromosomemec(SCCmec) element compriseddcs,Q9XB68-dcs,mvaS-SCC,Q5HJW6,dru,ugpQ,ydeM,mecA-mecR-mecI, txbimecI,tnpIS431,copA2-mco(copper resistance),ydhK,arsC-arsB-arsR(arsenic resistance), open reading frame PT43, andper-2. Recombinase genes,xylR(mecR2), and PSM-mec(phenol-soluble modulin) were absent. We suggest thatmeccomplex A should be split into two subtypes. One harbors PSM-mecandxylR(mecR2). It is found in SCCmectypes II, III, and VIII. The second subtype, described herein, is present in WA MRSA-59 and some coagulase-negative staphylococci.

scholarly journals Antimicrobial Activity of Ceftaroline Tested against Staphylococci with Reduced Susceptibility to Linezolid, Daptomycin, or Vancomycin from U.S. Hospitals, 2008 to 2011

2013 ◽  
Vol 57 (7) ◽  
pp. 3178-3181 ◽  
Author(s):  
Helio S. Sader ◽  
Robert K. Flamm ◽  
Ronald N. Jones
Keyword(s):  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Content Type ◽  
Microdilution Method ◽  
Medical Centers ◽  
Broth Microdilution Method ◽  
Valuable Treatment

ABSTRACTVancomycin, linezolid, and daptomycin are very active against staphylococci, but isolates with decreased susceptibility to these antimicrobial agents are isolated sporadically. A total of 19,350Staphylococcus aureusisolates (51% methicillin resistant [MRSA]) and 3,270 coagulase-negative staphylococci (CoNS) were collected consecutively from 82 U.S. medical centers from January 2008 to December 2011 and tested for susceptibility against ceftaroline and comparator agents by the reference broth microdilution method. AmongS. aureusstrains, 14 isolates (0.07%) exhibited decreased susceptibility to linezolid (MIC, ≥8 μg/ml), 18 (0.09%) to daptomycin (MIC, ≥2 μg/ml), and 369 (1.9%) to vancomycin (MIC, ≥2 μg/ml; 368 isolates at 2 μg/ml and 1 at 4 μg/ml). Fifty-one (1.6%) CoNS were linezolid resistant (MIC, ≥8 μg/ml), and four (0.12%) were daptomycin nonsusceptible (MIC, ≥2 μg/ml). Ceftaroline was very active againstS. aureusoverall (MIC50/90, 0.5/1 μg/ml; 98.5% susceptible), including MRSA (MIC50/90, 0.5/1 μg/ml; 97.2% susceptible). All daptomycin-nonsusceptible and 85.7% of linezolid-resistantS. aureusisolates were susceptible to ceftaroline. AgainstS. aureusisolates with a vancomycin MIC of ≥2 μg/ml, 91.9, 96.2, and 98.9% were susceptible to ceftaroline, daptomycin, and linezolid, respectively. CoNS strains were susceptible to ceftaroline (MIC50/90, 0.25/0.5 μg/ml; 99.1% inhibited at ≤1 μg/ml), including methicillin-resistant (MIC50/90, 0.25/0.5 μg/ml), linezolid-resistant (MIC50/90, 0.5/0.5 μg/ml), and daptomycin-nonsusceptible (4 isolates; MIC range, 0.03 to 0.12 μg/ml) strains. In conclusion, ceftaroline demonstrated potentin vitroactivity against staphylococci with reduced susceptibility to linezolid, daptomycin, or vancomycin, and it may represent a valuable treatment option for infections caused by these multidrug-resistant staphylococci.

scholarly journals The Novel Phage-Derived Antimicrobial Agent HY-133 Is Active against Livestock-Associated Methicillin-ResistantStaphylococcus aureus

2018 ◽  
Vol 62 (7) ◽  
Author(s):  
Ursula Kaspar ◽  
Jorge A. de Haro Sautto ◽  
Sonja Molinaro ◽  
Georg Peters ◽  
Evgeny A. Idelevich ◽  
...  
Keyword(s):  
Health Care ◽  
Staphylococcus Aureus ◽  
Animal Health ◽  
Active Agent ◽  
The Novel ◽  
Large Collection ◽  
Content Type ◽  
Health Care Settings ◽  
Bacteriophage Endolysin

ABSTRACTLivestock-associated methicillin-resistantStaphylococcus aureus(LA-MRSA) isolates are increasingly migrating from livestock into human and animal health care settings. Alternative substances are needed to overcome the drawbacks of currently available drugs used for MRSA eradication. The recombinant bacteriophage endolysin HY-133 has proved to be an active agent againstS. aureus. Here, thein vitroactivity of HY-133 was studied against a large collection of genetically diverse LA-MRSA isolates revealing its high activity againstmecA-,mecB-, andmecC-positive LA-MRSA.

scholarly journals Pharmacological Properties of the Marine Natural Product Marinopyrrole A against Methicillin-Resistant Staphylococcus aureus

2011 ◽  
Vol 55 (7) ◽  
pp. 3305-3312 ◽  
Author(s):  
Nina M. Haste ◽  
Chambers C. Hughes ◽  
Dan N. Tran ◽  
William Fenical ◽  
Paul R. Jensen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Effect ◽  
Inhibitory Effect ◽  
Marine Natural Product ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mammalian Cell Lines ◽  
Antistaphylococcal Activity ◽  
New Antibiotics ◽  
Mrsa Strains

ABSTRACTThe ongoing spread of methicillin-resistantStaphylococcus aureus(MRSA) strains in hospital and community settings presents a great challenge to public health and illustrates the urgency of discovering new antibiotics. Marinopyrrole A is a member of a structurally novel class of compounds identified from a species of marine-derived streptomycetes with evidence of antistaphylococcal activity. We show that marinopyrrole A has potent concentration-dependent bactericidal activity against clinically relevant hospital- and community-acquired MRSA strains, a prolonged postantibiotic effect superior to that of the current first-line agents vancomycin and linezolid, and a favorable resistance profile. Marinopyrrole A showed limited toxicity to mammalian cell lines (at >20× MIC). However, its antibiotic activity against MRSA was effectively neutralized by 20% human serum. A variety of marinopyrrole analogs were isolated from culture or synthetically produced to try to overcome the inhibitory effect of serum. While many of these compounds retained potent bactericidal effect against MRSA, their activities were also inhibited by serum. Marinopyrrole A has significant affinity for plastic and may therefore have potential as a potent anti-MRSA agent in cutaneous, intracatheter, or antibiotic-lock applications.

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