Livestock-associated Staphylococcus aureus CC398: Animal reservoirs and human infections

2014 ◽  
Vol 21 ◽  
pp. 523-530 ◽  
Author(s):  
Erwin Verkade ◽  
Jan Kluytmans
2019 ◽  
Vol 68 (1) ◽  
pp. 93-104
Author(s):  
KLAUDIA LISOWSKA-ŁYSIAK ◽  
MAJA KOSECKA-STROJEK ◽  
JOANNA BIAŁECKA ◽  
ANDRZEJ KASPROWICZ ◽  
KATARZYNA GARBACZ ◽  
...  

2021 ◽  
Vol 14 (4) ◽  
pp. 325
Author(s):  
David Sáez Moreno ◽  
Zehra Visram ◽  
Michele Mutti ◽  
Marcela Restrepo-Córdoba ◽  
Susana Hartmann ◽  
...  

Due to the rapid spread of antibiotic resistance, and the difficulties of treating biofilm-associated infections, alternative treatments for S. aureus infections are urgently needed. We tested the lytic activity of several wild type phages against a panel of 110 S. aureus strains (MRSA/MSSA) composed to reflect the prevalence of S. aureus clonal complexes in human infections. The plaquing host ranges (PHR) of the wild type phages were in the range of 51% to 60%. We also measured what we called the kinetic host range (KHR), i.e., the percentage of strains for which growth in suspension was suppressed for 24 h. The KHR of the wild type phages ranged from 2% to 49%, substantially lower than the PHRs. To improve the KHR and other key pharmaceutical properties, we bred the phages by mixing and propagating cocktails on a subset of S. aureus strains. These bred phages, which we termed evolution-squared (ε2) phages, have broader KHRs up to 64% and increased virulence compared to the ancestors. The ε2-phages with the broadest KHR have genomes intercrossed from up to three different ancestors. We composed a cocktail of three ε2-phages with an overall KHR of 92% and PHR of 96% on 110 S. aureus strains and called it PM-399. PM-399 has a lower propensity to resistance formation than the standard of care antibiotics vancomycin, rifampicin, or their combination, and no resistance was observed in laboratory settings (detection limit: 1 cell in 1011). In summary, ε2-phages and, in particular PM-399, are promising candidates for an alternative treatment of S. aureus infections.


2015 ◽  
Vol 59 (5) ◽  
pp. 2583-2587 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Nachum Kaplan ◽  
Ronald N. Jones ◽  
David J. Farrell

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.


Nature ◽  
2021 ◽  
Author(s):  
John A. Lednicky ◽  
Massimiliano S. Tagliamonte ◽  
Sarah K. White ◽  
Maha A. Elbadry ◽  
Md. Mahbubul Alam ◽  
...  

AbstractCoronaviruses have caused three major epidemics since 2003, including the ongoing SARS-CoV-2 pandemic. In each case, the emergence of coronavirus in our species has been associated with zoonotic transmissions from animal reservoirs1,2, underscoring how prone such pathogens are to spill over and adapt to new species. Among the four recognized genera of the family Coronaviridae, human infections reported so far have been limited to alphacoronaviruses and betacoronaviruses3–5. Here we identify porcine deltacoronavirus strains in plasma samples of three Haitian children with acute undifferentiated febrile illness. Genomic and evolutionary analyses reveal that human infections were the result of at least two independent zoonoses of distinct viral lineages that acquired the same mutational signature in the genes encoding Nsp15 and the spike glycoprotein. In particular, structural analysis predicts that one of the changes in the spike S1 subunit, which contains the receptor-binding domain, may affect the flexibility of the protein and its binding to the host cell receptor. Our findings highlight the potential for evolutionary change and adaptation leading to human infections by coronaviruses outside of the previously recognized human-associated coronavirus groups, particularly in settings where there may be close human–animal contact.


2020 ◽  
Author(s):  
M. R. Tuttobene ◽  
J. F. Pérez ◽  
E. Pavesi ◽  
B. Perez Mora ◽  
D. Biancotti ◽  
...  

Light sensing has been extensively characterized in the human pathogen Acinetobacter baumannii at environmental temperatures. However, the influence of light on the physiology and pathogenicity of human bacterial pathogens at temperatures found in warm-blooded hosts is still poorly understand. In this work, we show that ESKAPE priority pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter spp., which have been recognized by the WHO and the CDC as critical, can also sense and respond to light at temperatures found in human hosts. Most interestingly, in these pathogens light modulates important pathogenicity determinants as well as virulence in an epithelial infection model, which could have implications in human infections. In fact, we found that alpha-toxin-dependent hemolysis, motility and growth under iron deprived conditions are modulated by light in S. aureus. Light also regulates persistence, metabolism and the ability to kill competitors, in some of these microorganisms. Finally, light exerts a profound effect on the virulence of these pathogens in an epithelial infection model, though the response is not the same in the different species: virulence was enhanced by light in A. baumannii and S. aureus, while in A. nosocomialis and P. aeruginosa it was reduced. Neither the BlsA photoreceptor nor the type VI secretion system (T6SS) are involved in virulence modulation by light in A. baumannii. Overall, this fundamental knowledge highlights the potential use of light to control pathogen's virulence, either directly or by manipulating the light regulatory switch toward the lowest virulence/persistence configuration. IMPORTANCE Pathogenic bacteria are microorganisms capable of producing disease. Dangerous bacterial pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii are responsible for serious intrahospital and community infections in humans. Therapeutics is often complicated due to resistance to multiple antibiotics, rendering them ineffective. In this work, we show that these pathogens sense natural light and respond to it by modulating aspects related to their ability to cause disease: in the presence of light some of them become more aggressive while others show an opposite response. Overall, we provide new understanding on the behavior of these pathogens, which could contribute to control infections caused by them. Since the response is distributed in diverse pathogens, this notion could prove a general concept.


Toxins ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 500 ◽  
Author(s):  
Assia Mairi ◽  
Abdelaziz Touati ◽  
Alix Pantel ◽  
Karima Zenati ◽  
Alex Yahiaoui Martinez ◽  
...  

The diffusion of Panton–Valentine leukocidin (PVL)–positive methicillin-resistant S. aureus (MRSA) is a health problem in Algeria. The objectives of the study were to investigate the global distribution of methicillin-susceptible S. aureus (MSSA) and MRSA isolates in different ecological niches in this country. In total, 2246 samples were collected from humans, livestock, wild animals, pets, food products and the aquatic environment, from 12 Algerian provinces. A total of 312 S. aureus were detected from 2446 samples (12.7%) in the screened niches. We observed the emergence of toxinogenic S. aureus representing 41% of the isolates. Among them, we noted the diffusion of ST80-IV CA-MRSA PVL + strains isolated in human, animals, and food and genetic diversity of MSSA PVL + isolates. This study suggests an alarming dissemination of MRSA-ST80 PVL + in both human and extra-human sources in Algeria. Moreover, MSSA may become a permanent reservoir of the PVL genes necessary for human infections.


2021 ◽  
Author(s):  
Marta Matuszewska ◽  
Gemma G. R. Murray ◽  
Xiaoliang Ba ◽  
Rhiannon Wood ◽  
Mark A Holmes ◽  
...  

Mobile genetic elements (MGEs) often carry genes that benefit their bacterial hosts. In methicillin-resistant Staphylococcus aureus (MRSA), MGEs have been associated with antibiotic resistance, virulence, and host adaptation. Clonal-complex (CC) 398 is the dominant MRSA in European livestock, and a growing cause of human infections. To understand the risk posed by livestock-associated MRSA to human health, we have used a collection of 1,180 CC398 genomes, sampled from several livestock species and humans, with a broad geographic distribution and spanning 27 years, to reconstruct the dynamics of the MGEs. We find that the emergence of livestock-associated CC398 coincided with the acquisition of a Tn916 transposon carrying a tetracycline resistance gene, which has been stably vertically inherited for 57 years. This was followed by the acquisition of a large SCCmec type V element that carries methicillin, tetracycline and heavy metal resistance genes. This has been maintained within livestock-associated CC398 for at least 35 years, with occasional truncations and replacements with other, smaller type IV SCCmec elements. In contrast, a class of prophages that carry a human immune-evasion gene cluster, that are largely absent from livestock-associated CC398, have been repeatedly gained and lost across both human- and livestock-associated CC398. The variable dynamics of these three MGEs means that when livestock-associated MRSA infects humans, re-adaptation to the human host outpaces the loss of antibiotic resistance. Moreover, the stability of both Tn916 and SCCmec suggests that they may persist despite ongoing reductions in antibiotic and zinc oxide use in farming.


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