An Actinobacterial Isolate, Streptomyces sp. YX44, Produces Broad-Spectrum Antibiotics That Strongly Inhibit Staphylococcus aureus

The need for new antibiotics is increasing due to their overuse, and antibiotic resistance has become one of the major threats worldwide to public health, food safety, and clinical treatment. In this study, we describe an actinobacterial isolate, YX44, which belongs to the genus Streptomyces. This Streptomyces was isolated from a drinking pipe located in Osaka, Japan, and has the ability to inhibit Gram-positive bacteria, Gram-negative bacteria, and various fungi. YX44 fermentation broth shows strong activity against Escherichia coli and Staphylococcus aureus, as well as also inhibiting clinical isolates of multidrug-resistant Staphylococcus aureus. The YX44 antibacterial substances in the broth are relatively heat-stable, show high stability from the pH range 1 to 11, and have good solubility in both organic and non-organic solvents. Size-exclusion chromatography revealed that the YX44 antibacterial compounds are less than 1000 Da in size. LC-MS was able to identify three possible candidate molecules with molecular weights of 308, 365, 460, and 653 g/mol; none of these sizes correspond to any well-known antibiotics. Our results show that Streptomyces sp. YX44 seems to produce a number of novel antibiotics with high pH stability and good solubility that have significant activity against S. aureus, including multidrug-resistant strains.

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Activity of Debio1452, a FabI Inhibitor with Potent Activity against Staphylococcus aureus and Coagulase-Negative Staphylococcus spp., Including Multidrug-Resistant Strains

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05119-14 ◽

2015 ◽

Vol 59 (5) ◽

pp. 2583-2587 ◽

Cited By ~ 20

Author(s):

Robert K. Flamm ◽

Paul R. Rhomberg ◽

Nachum Kaplan ◽

Ronald N. Jones ◽

David J. Farrell

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Agents ◽

Fatty Acid Biosynthesis ◽

Multidrug Resistant ◽

Coagulase Negative Staphylococcus ◽

Significant Activity ◽

Coagulase Negative Staphylococci ◽

Content Type ◽

Mrsa Strains ◽

Human Infections

ABSTRACTStaphylococcus aureusand coagulase-negative staphylococci (CoNS) are responsible for a wide variety of human infections. The investigational antibacterial Debio1450 (previously AFN-1720), a prodrug of Debio1452 (previously AFN-1252), specifically targets staphylococci without significant activity against other Gram-positive or Gram-negative species. Debio1452 inhibits FabI, an enzyme critical to fatty acid biosynthesis in staphylococci. The activity of Debio1452 against CoNS, methicillin-susceptibleS. aureus(MSSA), and methicillin-resistantS. aureus(MRSA), including significant clones, was determined. A globally diverse collection of 574 patient isolates from 35 countries was tested that included CoNS (6 species, 103 strains), MSSA (154 strains), MRSA (163 strains), and molecularly characterized strains (includingspa-typed MRSA clones; 154 strains). The isolates were tested for susceptibility by CLSI broth microdilution methods against Debio1452 and 10 comparators. The susceptibility rates for the comparators were determined using CLSI and EUCAST breakpoint criteria. AllS. aureusand CoNS strains were inhibited by Debio1452 concentrations of ≤0.12 and ≤0.5 μg/ml, respectively. The MIC50s for MSSA, MRSA, and molecularly characterized MRSA strains were 0.004 μg/ml, and the MIC90s ranged from 0.008 to 0.03 μg/ml. The MICs were higher for the CoNS isolates (MIC50/90, 0.015/0.12 μg/ml). AmongS. aureusstrains, resistance was common for erythromycin (61.6%), levofloxacin (49.0%), clindamycin (27.6%), tetracycline (15.7%), and trimethoprim-sulfamethoxazole (7.0%). Debio1452 demonstrated potent activity against MSSA, MRSA, and CoNS. Debio1452 showed significantly greater activity overall (MIC50, 0.004 μg/ml) than the other agents tested against these staphylococcal species, which included dominant MRSA clones and strains resistant to currently utilized antimicrobial agents.

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Streptomyces sp. AT37 isolated from a Saharan soil produces a furanone derivative active against multidrug-resistant Staphylococcus aureus

World Journal of Microbiology and Biotechnology ◽

10.1007/s11274-017-2265-y ◽

2017 ◽

Vol 33 (6) ◽

Cited By ~ 7

Author(s):

El Hadj Driche ◽

Nasserdine Sabaou ◽

Christian Bijani ◽

Abdelghani Zitouni ◽

Frédéric Pont ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Multidrug Resistant ◽

Streptomyces Sp ◽

Saharan Soil

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Faculty Opinions recommendation of Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone USA300 in men who have sex with men.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1102146.558131 ◽

2008 ◽

Author(s):

J Michael Kilby

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Multidrug Resistant ◽

Methicillin Resistant ◽

Sex With Men

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The Prevalence of Virulence Determinants and Antibiotic Resistance Patterns in Methicillin—Resistant Staphylococcus aureus in a Nursing Home in Poland

Pathogens ◽

10.3390/pathogens10040427 ◽

2021 ◽

Vol 10 (4) ◽

pp. 427

Author(s):

Martyna Kasela ◽

Agnieszka Grzegorczyk ◽

Bożena Nowakowicz-Dębek ◽

Anna Malm

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Variable Number Tandem Repeat ◽

Multidrug Resistant ◽

Variable Number ◽

Pulse Field ◽

Virulence Determinants ◽

Gene Encoding ◽

Methicillin Resistant ◽

Pulse Field Gel Electrophoresis

Nursing homes (NH) contribute to the regional spread of methicillin-resistant Staphylococcus aureus (MRSA). Moreover, residents are vulnerable to the colonization and subsequent infection of MRSA etiology. We aimed at investigating the molecular and phenotypic characteristics of 21 MRSA collected from the residents and personnel in an NH (Lublin, Poland) during 2018. All MRSA were screened for 20 genes encoding virulence determinants (sea-see, eta, etb, tst, lukS-F-PV, eno, cna, ebpS, fib, bbp, fnbA, fnbB, icaADBC) and for resistance to 18 antimicrobials. To establish the relatedness and clonal complexes of MRSA in NH we applied multiple-locus variable-number tandem-repeat fingerprinting (MLVF), pulse field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. We identified four sequence types (ST) among two clonal complexes (CC): ST (CC22) known as EMRSA-15 as well as three novel STs—ST6295 (CC8), ST6293 (CC8) and ST6294. All tested MRSA were negative for sec, eta, etb, lukS-F-PV, bbp and ebpS genes. The most prevalent gene encoding toxin was sed (52.4%; n = 11/21), and adhesins were eno and fnbA (100%). Only 9.5% (n = 2/21) of MRSA were classified as multidrug-resistant. The emergence of novel MRSA with a unique virulence and the presence of epidemic clone EMRSA-15 creates challenges for controlling the spread of MRSA in NH.

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Spectral and Antibiotic Susceptibility of Pathogens Isolated from Saudi Patients with Diabetic Foot Infections

Microbiology Research ◽

10.3390/microbiolres12010002 ◽

2021 ◽

Vol 12 (1) ◽

pp. 16-20

Author(s):

Samiah Hamad S Al-Mijalli

Keyword(s):

Staphylococcus Aureus ◽

Diabetic Foot ◽

Antibiotic Susceptibility ◽

Empirical Therapy ◽

Multidrug Resistant ◽

Foot Ulcers ◽

Sensitivity Testing ◽

Cross Sectional ◽

Diabetic Foot Infections ◽

Microbiological Methods

Diabetic foot infections (DFIs) are a significant health issue and a common complication among patients with diabetes. To develop antibiotic therapy for these high-risk patients, the current study evaluates the scope of DFIs and identifies the causing microbes. It also measures spectrum and antibiotic susceptibility of the pathogens isolated from adults with DFIs in Saudi Arabia. To achieve the study objectives, a cross-sectional study was implemented and the baseline characteristics for 44 patients with DFIs were defined. Optimal aerobic and anaerobic microbiological techniques were utilized to culture specimens isolated from infected foot ulcers. The standard microbiological methods were employed to identify the bacterial isolates and antibiotic susceptibility testing was conducted following the procedures of the Clinical and Laboratory Standards Institute (CLSI). Results showed that 12 microorganisms were isolated from the participants’ diabetic foot ulcers. Staphylococcus Aureus was ranked first because it appeared in 29 (65.9%) cases. Streptococcus Agalactiae was ranked second and multi-microbial infections were also found. Most of the organisms were susceptible to Vancomycin, Ciprofloxacin, and Cefalexin, but they were resistant to Methicillin, Gentamicin, and Ampicillin antibiotics. Staphylococcus Aureus was most sensitive to Ciprofloxacin, while it was resistant to Methicillin. About 10% of the isolates were multidrug-resistant. The study concludes that while Vancomycin should be used empirically for Gram-positive isolates, Ciprofloxacin can be taken into consideration for most of the Gram-negatives aerobes. Based on including various microorganisms and the advent of multidrug-resistant strains, proper culture and sensitivity testing are necessary prior to the empirical therapy.

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Successful Treatment of Staphylococcus aureus Prosthetic Joint Infection with Bacteriophage Therapy

Viruses ◽

10.3390/v13061182 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1182

Author(s):

Claudia Ramirez-Sanchez ◽

Francis Gonzales ◽

Maureen Buckley ◽

Biswajit Biswas ◽

Matthew Henry ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Prosthetic Joint Infection ◽

Joint Infection ◽

Multidrug Resistant ◽

Successful Outcome ◽

Prolonged Treatment ◽

Lytic Phage ◽

Bacteriophage Therapy ◽

Prosthetic Joint ◽

Knee Joint Infection

Successful joint replacement is a life-enhancing procedure with significant growth in the past decade. Prosthetic joint infection occurs rarely; it is a biofilm-based infection that is poorly responsive to antibiotic alone. Recent interest in bacteriophage therapy has made it possible to treat some biofilm-based infections, as well as those caused by multidrug-resistant pathogens, successfully when conventional antibiotic therapy has failed. Here, we describe the case of a 61-year-old woman who was successfully treated after a second cycle of bacteriophage therapy administered at the time of a two-stage exchange procedure for a persistent methicillin-sensitive Staphylococcus aureus (MSSA) prosthetic knee-joint infection. We highlight the safety and efficacy of both intravenous and intra-articular infusions of bacteriophage therapy, a successful outcome with a single lytic phage, and the development of serum neutralization with prolonged treatment.

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Development of Advanced Chimeric Endolysin to Control Multidrug-Resistant Staphylococcus aureus through Domain Shuffling

ACS Infectious Diseases ◽

10.1021/acsinfecdis.0c00812 ◽

2021 ◽

Author(s):

Chanyoung Lee ◽

Jinwoo Kim ◽

Bokyung Son ◽

Sangryeol Ryu

Keyword(s):

Staphylococcus Aureus ◽

Multidrug Resistant ◽

Domain Shuffling

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Ammonia Production by Streptomyces Symbionts of Acromyrmex Leaf-Cutting Ants Strongly Inhibits the Fungal Pathogen Escovopsis

Microorganisms ◽

10.3390/microorganisms9081622 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1622

Author(s):

Basanta Dhodary ◽

Dieter Spiteller

Keyword(s):

Fungal Pathogen ◽

Closed Loop ◽

Pathogenic Fungus ◽

Ant Colonies ◽

Strong Activity ◽

Streptomyces Sp ◽

Mutualistic Symbiosis ◽

Leaf Cutting ◽

Leucoagaricus Gongylophorus ◽

Production Of Ammonia

Leaf-cutting ants live in mutualistic symbiosis with their garden fungus Leucoagaricus gongylophorus that can be attacked by the specialized pathogenic fungus Escovopsis. Actinomyces symbionts from Acromyrmex leaf-cutting ants contribute to protect L. gongylophorus against pathogens. The symbiont Streptomyces sp. Av25_4 exhibited strong activity against Escovopsis weberi in co-cultivation assays. Experiments physically separating E. weberi and Streptomyces sp. Av25_4 allowing only exchange of volatiles revealed that Streptomyces sp. Av25_4 produces a volatile antifungal. Volatile compounds from Streptomyces sp. Av25_4 were collected by closed loop stripping. Analysis by NMR revealed that Streptomyces sp. Av25_4 overproduces ammonia (up to 8 mM) which completely inhibited the growth of E. weberi due to its strong basic pH. Additionally, other symbionts from different Acromyrmex ants inhibited E. weberi by production of ammonia. The waste of ca. one third of Acomyrmex and Atta leaf-cutting ant colonies was strongly basic due to ammonia (up to ca. 8 mM) suggesting its role in nest hygiene. Not only complex and metabolically costly secondary metabolites, such as polyketides, but simple ammonia released by symbionts of leaf-cutting ants can contribute to control the growth of Escovopsis that is sensitive to ammonia in contrast to the garden fungus L. gongylophorus.

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