scholarly journals Bacteriocins of Non-aureus Staphylococci Isolated from Bovine Milk

2017 ◽  
Vol 83 (17) ◽  
Author(s):  
Domonique A. Carson ◽  
Herman W. Barkema ◽  
Sohail Naushad ◽  
Jeroen De Buck
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Genome Mining ◽  
Bovine Milk ◽  
Gene Clusters ◽  
Antibiotic Use ◽  
Content Type ◽  
Treatment And Prevention ◽  
Whole Genomes

ABSTRACT Non-aureus staphylococci (NAS), the bacteria most commonly isolated from the bovine udder, potentially protect the udder against infection by major mastitis pathogens due to bacteriocin production. In this study, we determined the inhibitory capability of 441 bovine NAS isolates (comprising 26 species) against bovine Staphylococcus aureus. Furthermore, inhibiting isolates were tested against a human methicillin-resistant S. aureus (MRSA) isolate using a cross-streaking method. We determined the presence of bacteriocin clusters in NAS whole genomes using genome mining tools, BLAST, and comparison of genomes of closely related inhibiting and noninhibiting isolates and determined the genetic organization of any identified bacteriocin biosynthetic gene clusters. Forty isolates from 9 species (S. capitis, S. chromogenes, S. epidermidis, S. pasteuri, S. saprophyticus, S. sciuri, S. simulans, S. warneri, and S. xylosus) inhibited growth of S. aureus in vitro, 23 isolates of which, from S. capitis, S. chromogenes, S. epidermidis, S. pasteuri, S. simulans, and S. xylosus, also inhibited MRSA. One hundred five putative bacteriocin gene clusters encompassing 6 different classes (lanthipeptides, sactipeptides, lasso peptides, class IIa, class IIc, and class IId) in 95 whole genomes from 16 species were identified. A total of 25 novel bacteriocin precursors were described. In conclusion, NAS from bovine mammary glands are a source of potential bacteriocins, with >21% being possible producers, representing potential for future characterization and prospective clinical applications. IMPORTANCE Mastitis (particularly infections caused by Staphylococcus aureus) costs Canadian dairy producers $400 million/year and is the leading cause of antibiotic use on dairy farms. With increasing antibiotic resistance and regulations regarding use, there is impetus to explore bacteriocins (bacterially produced antimicrobial peptides) for treatment and prevention of bacterial infections. We examined the ability of 441 NAS bacteria from Canadian bovine milk samples to inhibit growth of S. aureus in the laboratory. Overall, 9% inhibited growth of S. aureus and 58% of those also inhibited MRSA. In NAS whole-genome sequences, we identified >21% of NAS as having bacteriocin genes. Our study represents a foundation to further explore NAS bacteriocins for clinical use.

scholarly journals Efficacy of Bacteriophages Against Staphylococcus aureus Isolates from Bovine Mastitis

2020 ◽  
Vol 13 (3) ◽  
pp. 35 ◽  
Author(s):  
Isabel Titze ◽  
Tatiana Lehnherr ◽  
Hansjörg Lehnherr ◽  
Volker Krömker
Keyword(s):  
Staphylococcus Aureus ◽  
Host Range ◽  
Bacterial Infections ◽  
Plaque Assay ◽  
Bovine Milk ◽  
Bovine Mastitis ◽  
Raw Milk ◽  
Pasteurized Milk

The lytic efficacy of bacteriophages against Staphylococcus aureus isolates from bovine milk was investigated in vitro, regarding possible applications in the therapy of udder inflammation caused by bacterial infections (mastitis). The host range of sequenced, lytic bacteriophages was determined against a collection of 92 Staphylococcus (S.) aureus isolates. The isolates originated from quarter foremilk samples of clinical and subclinical mastitis cases. A spot test and a subsequent plaque assay were used to determine the phage host range. According to their host range, propagation and storage properties, three phages, STA1.ST29, EB1.ST11, and EB1.ST27, were selected for preparing a bacteriophage mixture (1:1:1), which was examined for its lytic activity against S. aureus in pasteurized and raw milk. It was found that almost two thirds of the isolates could be lysed by at least one of the tested phages. The bacteriophage mixture was able to reduce the S. aureus germ density in pasteurized milk and its reduction ability was maintained in raw milk, with only a moderate decrease compared to the results in pasteurized milk. The significant reduction ability of the phage mixture in raw milk promotes further in vivo investigation.

scholarly journals In VitroStudies Indicate a High Resistance Potential for the Lantibiotic Nisin in Staphylococcus aureus and Define a Genetic Basis for Nisin Resistance

2011 ◽  
Vol 55 (5) ◽  
pp. 2362-2368 ◽  
Author(s):  
Katy L. Blake ◽  
Chris P. Randall ◽  
Alex J. O'Neill
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Fold Increase ◽  
Peptide Antibiotics ◽  
Uncharacterized Protein ◽  
Content Type ◽  
Development Of Resistance ◽  
Genes Encoding ◽  
Bacterial Fitness

ABSTRACTLantibiotics such as nisin (NIS) are peptide antibiotics that may have a role in the chemotherapy of bacterial infections. A perceived benefit of lantibiotics for clinical use is their low propensity to select resistance, although detailed resistance studies with relevant bacterial pathogens are lacking. Here we examined the development of resistance to NIS inStaphylococcus aureus, establishing that mutants, including small-colony variants, exhibiting substantial (4- to 32-fold) reductions in NIS susceptibility could be selected readily. Comparative genome sequencing of a single NISrmutant exhibiting a 32-fold increase in NIS MIC revealed the presence of only two mutations, leading to the substitutions V229G in the purine operon repressor, PurR, and A208E in an uncharacterized protein encoded by SAOUHSC_02955. Independently selected NISrmutants also harbored mutations in the genes encoding these products. Reintroduction of these mutations into theS. aureuschromosome alone and in combination revealed that SAOUHSC_02955(A208E) made the primary contribution to the resistance phenotype, conferring up to a 16-fold decrease in NIS susceptibility. Bioinformatic analyses suggested that this gene encodes a sensor histidine kinase, leading us to designate it “nisin susceptibility-associated sensor (nsaS).” Doubling-time determinations and mixed-culture competition assays between NISrand NISsstrains indicated that NIS resistance had little impact on bacterial fitness, and resistance was stable in the absence of selection. The apparent ease with whichS. aureuscan develop and maintain NIS resistancein vitrosuggests that resistance to NIS and other lantibiotics with similar modes of action would arise in the clinic if these agents are employed as chemotherapeutic drugs.

scholarly journals Topical Antibiotic Use Coselects for the Carriage of Mobile Genetic Elements Conferring Resistance to Unrelated Antimicrobials in Staphylococcus aureus

2017 ◽  
Vol 62 (2) ◽  
Author(s):  
Glen P. Carter ◽  
Mark B. Schultz ◽  
Sarah L. Baines ◽  
Anders Gonçalves da Silva ◽  
Helen Heffernan ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
New Zealand ◽  
Single Molecule ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Topical Antibiotic ◽  
Content Type ◽  
Topical Antibiotics ◽  
The Impact

ABSTRACTTopical antibiotics, such as mupirocin and fusidic acid, are commonly used in the prevention and treatment of skin infections, particularly those caused by staphylococci. However, the widespread use of these agents is associated with increased resistance to these agents, potentially limiting their efficacy. Of particular concern is the observation that resistance to topical antibiotics is often associated with multidrug resistance, suggesting that topical antibiotics may play a role in the emergence of multidrug-resistant (MDR) strains. New Zealand (NZ) has some of the highest globally recorded rates of topical antibiotic usage and resistance. Using a combination of Pacific Biosciences single-molecule real-time (SMRT) whole-genome sequencing, Illumina short-read sequencing, and Bayesian phylogenomic modeling on 118 new multilocus sequence type 1 (ST1) communityStaphylococcus aureusisolates from New Zealand and 61 publically available international ST1 genome sequences, we demonstrate a strong correlation between the clinical introduction of topical antibiotics and the emergence of MDR ST1S. aureus. We also providein vitroexperimental evidence showing that exposure to topical antibiotics can lead to the rapid selection of MDRS. aureusisolates carrying plasmids that confer resistance to multiple unrelated antibiotics, from within a mixed population of competitor strains. These findings have important implications regarding the impact of the indiscriminate use of topical antibiotics.

scholarly journals Staphylococcus aureus Protein A Promotes Immune Suppression

mBio ◽  
2013 ◽  
Vol 4 (5) ◽  
Author(s):  
Scott D. Kobayashi ◽  
Frank R. DeLeo
Keyword(s):  
Staphylococcus Aureus ◽  
B Cell ◽  
Immune Evasion ◽  
Bacterial Infections ◽  
Binding Capacity ◽  
Protein A ◽  
Strong Support ◽  
The United States ◽  
Content Type

ABSTRACTStaphylococcus aureusis a prominent cause of human infections worldwide and is notorious for its ability to acquire resistance to antibiotics. Methicillin-resistantS. aureus(MRSA), in particular, is endemic in hospitals and is the most frequent cause of community-associated bacterial infections in the United States. Inasmuch as treatment options for severe MRSA infections are limited, there is need for a vaccine that protects against such infections. However, recent efforts to generate a staphylococcal vaccine have met with little success in human clinical trials. These failures are somewhat puzzling, since the vaccine antigens tested promote opsonophagocytosisin vitroand confer protection in animal infection models. One possibility is that the pathogen inhibits (and/or fails to elicit) the development of protective immunity in humans. Indeed,S. aureusproduces numerous molecules that can potentially promote immune evasion, including protein A (SpA), an immunoglobulin (Ig)-binding protein present on the bacterial surface and freely secreted into the extracellular environment. SpA binds the Fc region of antibody and the Fab regions of the B-cell receptor, processes that are known to block opsonophagocytosis and cause B-cell deathin vitro. In a recent study, Falugi et al. [F. Falugi, H. K. Kim, D. M. Missiakas, and O. Schneewind, mBio 4(5):e00575-13, 2013] showed that vaccination withspamutantS. aureusstrains lacking antibody Fc- and/or Fab-binding capacity protects against subsequent challenge with the USA300 epidemic strain. The findings provide strong support for the idea that SpA promotesS. aureusimmune evasionin vivoand form the foundation for a new approach in our efforts to develop a vaccine that prevents severeS. aureusinfections.

scholarly journals A Human Biofilm-Disrupting Monoclonal Antibody Potentiates Antibiotic Efficacy in Rodent Models of both Staphylococcus aureus and Acinetobacter baumannii Infections

2017 ◽  
Vol 61 (10) ◽  
Author(s):  
Yan Q. Xiong ◽  
Angeles Estellés ◽  
L. Li ◽  
W. Abdelhady ◽  
R. Gonzales ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Monoclonal Antibody ◽  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Bacterial Species ◽  
Human Monoclonal Antibody ◽  
Extracellular Dna ◽  
Content Type

ABSTRACT Many serious bacterial infections are antibiotic refractory due to biofilm formation. A key structural component of biofilm is extracellular DNA, which is stabilized by bacterial proteins, including those from the DNABII family. TRL1068 is a high-affinity human monoclonal antibody against a DNABII epitope conserved across both Gram-positive and Gram-negative bacterial species. In the present study, the efficacy of TRL1068 for the disruption of biofilm was demonstrated in vitro in the absence of antibiotics by scanning electron microscopy. The in vivo efficacy of this antibody was investigated in a well-characterized catheter-induced aortic valve infective endocarditis model in rats infected with a methicillin-resistant Staphylococcus aureus (MRSA) strain with the ability to form thick biofilms, obtained from the blood of a patient with persistent clinical infection. Animals were treated with vancomycin alone or in combination with TRL1068. MRSA burdens in cardiac vegetations and within intracardiac catheters, kidneys, spleen, and liver showed significant reductions in the combination arm versus vancomycin alone (P < 0.001). A trend toward mortality reduction was also observed (P = 0.09). In parallel, the in vivo efficacy of TRL1068 against a multidrug-resistant clinical Acinetobacter baumannii isolate was explored by using an established mouse model of skin and soft tissue catheter-related biofilm infection. Catheter segments infected with A. baumannii were implanted subcutaneously into mice; animals were treated with imipenem alone or in combination with TRL1068. The combination showed a significant reduction of catheter-adherent bacteria versus the antibiotic alone (P < 0.001). TRL1068 shows excellent promise as an adjunct to standard-of-care antibiotics for a broad range of difficult-to-treat bacterial infections.

scholarly journals Heterogeneity of Genetic Pathways toward Daptomycin Nonsusceptibility in Staphylococcus aureus Determined by Adjunctive Antibiotics

2015 ◽  
Vol 59 (5) ◽  
pp. 2799-2806 ◽  
Author(s):  
Andrew D. Berti ◽  
Sarah L. Baines ◽  
Benjamin P. Howden ◽  
George Sakoulas ◽  
Victor Nizet ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Efficacy ◽  
Combined Exposure ◽  
Genetic Pathways ◽  
Methicillin Resistant ◽  
Content Type ◽  
Low Level ◽  
Whole Genomes ◽  
High Level

ABSTRACTDaptomycin is increasingly used in combination with other antibiotics to enhance antimicrobial efficacy and/or to mitigate the emergence of daptomycin nonsusceptibility (DNS). This study used a clinical methicillin-resistantStaphylococcus aureus(MRSA) strain in which DNS emerged upon therapy to examine the influence of antibiotic combinations on the development of mutations in specific genes (mprF,rpoBC,dltA,cls2, andyycFG) previously associated with DNS. Whole genomes of bacteria obtained following 28 days ofin vitroexposure to daptomycin with or without adjunctive clarithromycin, linezolid, oxacillin, or trimethoprim-sulfamethoxazole were sequenced, and the sequences were compared to that of the progenitor isolate. The addition of oxacillin to medium containing daptomycin prevented the emergence ofmprFmutation but did not preventrpoBCmutation (P< 0.01). These isolates maintained susceptibility to daptomycin during the combined exposure (median MIC, 1 mg/liter). Daptomycin plus clarithromycin or linezolid resulted in low-level (1.5 to 8 mg/liter) and high-level (12 to 96 mg/liter) DNS, respectively, and did not preventmprFmutation. However, these same combinations preventedrpoBCmutation. Daptomycin alone or combined with linezolid or trimethoprim-sulfamethoxazole resulted in high-level DNS and mutations inmprFplusrpoBC,cls2, andyycFG. Combining daptomycin with different antimicrobials alters the mutational space available for DNS development, thereby favoring the development of predictable collateral susceptibilities.

scholarly journals Combining the FtsZ-Targeting Prodrug TXA709 and the Cephalosporin Cefdinir Confers Synergy and Reduces the Frequency of Resistance in Methicillin-Resistant Staphylococcus aureus

2016 ◽  
Vol 60 (7) ◽  
pp. 4290-4296 ◽  
Author(s):  
Malvika Kaul ◽  
Lilly Mark ◽  
Ajit K. Parhi ◽  
Edmond J. LaVoie ◽  
Daniel S. Pilch
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Drug Dose ◽  
Drug Induced ◽  
Methicillin Resistant ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Emergence Of Resistance

ABSTRACTCombination therapy of bacterial infections with synergistic drug partners offers distinct advantages over monotherapy. Among these advantages are (i) a reduction of the drug dose required for efficacy, (ii) a reduced potential for drug-induced toxicity, and (iii) a reduced potential for the emergence of resistance. Here, we describe the synergistic actions of the third-generation oral cephalosporin cefdinir and TXA709, a new, FtsZ-targeting prodrug that we have developed with improved pharmacokinetics and enhancedin vivoefficacy against methicillin-resistantStaphylococcus aureus(MRSA) relative to earlier agents. We show that the active product of TXA709 (TXA707) acts synergistically with cefdinirin vitroagainst clinical isolates of MRSA, vancomycin-intermediateS. aureus(VISA), vancomycin-resistantS. aureus(VRSA), and linezolid-resistantS. aureus(LRSA). In addition, relative to TXA707 alone, the combination of TXA707 and cefdinir significantly reduces or eliminates the detectable emergence of resistance. We also demonstrate synergyin vivowith oral administration of the prodrug TXA709 and cefdinir in mouse models of both systemic and tissue (thigh) infections with MRSA. This synergy reduces the dose of TXA709 required for efficacy 3-fold. Viewed as a whole, our results highlight the potential of TXA709 and cefdinir as a promising combination for the treatment of drug-resistant staphylococcal infections.

scholarly journals Effects of Phage Endolysin SAL200 Combined with Antibiotics on Staphylococcus aureus Infection

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Nak-Hyun Kim ◽  
Wan Beom Park ◽  
Jeong Eun Cho ◽  
Yoon Jeong Choi ◽  
Su Jin Choi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Galleria Mellonella ◽  
Synergistic Effects ◽  
Splenic Tissue ◽  
Bacterial Density ◽  
Content Type ◽  
Time Kill

ABSTRACT Phages and their derivatives are increasingly being reconsidered for use in the treatment of bacterial infections due to the rising rates of antibiotic resistance. We assessed the antistaphylococcal effect of the endolysin SAL200 in combination with standard-of-care (SOC) antibiotics. The activity of SAL200 when it was combined with SOC antibiotics was assessed in vitro by checkerboard and time-kill assays and in vivo with murine bacteremia and Galleria mellonella infection models. SAL200 reduced the SOC antibiotic MICs and showed a ≥3-log10-CFU/ml reduction of Staphylococcus aureus counts within 30 min in time-kill assays. Combinations of SAL200 and SOC antibiotics achieved a sustained decrease of >2 log10 CFU/ml. SAL200 significantly lowered the blood bacterial density within 1 h by >1 log10 CFU/ml in bacteremic mice (P < 0.05 versus untreated mice), and SAL200 and SOC antibiotic combinations achieved the lowest levels of bacteremia. The bacterial density in splenic tissue at 72 h postinfection was the lowest in mice treated with SAL200 and SOC antibiotic combinations. SAL200 combined with SOC antibiotics also improved Galleria mellonella larva survival at 96 h postinfection. The combination of the phage endolysin SAL200 with SOC antistaphylococcal antibiotics showed synergistic effects in vitro and in vivo. The combination of SAL200 with SOC antibiotics could help in the treatment of difficult-to-treat S. aureus infections.

scholarly journals A Tick Antivirulence Protein Potentiates Antibiotics against Staphylococcus aureus

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Nabil M. Abraham ◽  
Lei Liu ◽  
Brandon L. Jutras ◽  
Kristen Murfin ◽  
Ali Acar ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Repeat Region ◽  
Methicillin Resistant ◽  
Content Type ◽  
Antifreeze Glycoprotein ◽  
Infection Models ◽  
New Strategies

ABSTRACT New strategies are needed to combat antibiotic resistance, especially against pathogens such as methicillin-resistant Staphylococcus aureus. A tick antifreeze glycoprotein, IAFGP, possesses potent antibiofilm properties against a variety of clinical pathogens, including S. aureus. Synergy between IAFGP, or a peptide (P1) representative of a repeat region of the protein, with different antibiotics was assessed in vitro. Antibiotics that synergized with either IAFPG or P1 were further evaluated in vivo using vertebrate and invertebrate infection models. IAFGP readily enhanced the efficacy of antibiotics against S. aureus. Synergy with daptomycin, an antibiotic used to treat methicillin-resistant S. aureus, was observed in vitro and in vivo using iafgp-transgenic mice and flies. Furthermore, synergy with ciprofloxacin or gentamicin, antibiotics not generally used to treat S. aureus, was also perceived. The combined effect of the antibiotic and IAFGP was associated with improved permeation of the antibiotic into the cell. Our results highlight that synergy of IAFGP with antibiotics traditionally used to treat this pathogen, and enhancement of the potency of antibiotics not commonly used against this microbe, can provide novel alternative therapeutic strategies to combat bacterial infections.

scholarly journals Exogenous Alginate Protects Staphylococcus aureus from Killing by Pseudomonas aeruginosa

2019 ◽  
Vol 202 (8) ◽  
Author(s):  
Courtney E. Price ◽  
Dustin G. Brown ◽  
Dominique H. Limoli ◽  
Vanessa V. Phelan ◽  
George A. O’Toole
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Physical Space ◽  
Late Time ◽  
Protective Effects ◽  
Content Type ◽  
Alginate Production ◽  
The Impact

ABSTRACT Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are monoinfected with either P. aeruginosa or S. aureus. We showed previously that mucoid strains of P. aeruginosa can coexist with S. aureus in vitro due to the transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here, we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm coculture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to the transcriptional downregulation of pvdA, a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS (Pseudomonas quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid P. aeruginosa with nonmucoid P. aeruginosa strains can mitigate the killing of S. aureus by the nonmucoid strain of P. aeruginosa, indicating that the mechanism that we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill S. aureus at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the S. aureus-protective effects of mucoidy in a strain-specific manner. IMPORTANCE CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are P. aeruginosa and S. aureus, with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus coexistence, despite evidence that P. aeruginosa kills S. aureus when these organisms are cocultured in vitro. Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.

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