Treatment of Staphylococcal Infections

Crossley, Kent; John, Joseph F.

doi:10.1002/9781444308464.ch31

Cited by 8 publications

(9 citation statements)

References 211 publications

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“…Replication of that circle would render horizontal transfer of SCC elements to new hosts more efficient by supplying multiple copies to start with. While horizontal transfer of SCC elements has been difficult to demonstrate in the lab, sequencing data clearly show that in the wild, at least some variants such as SCCmec types II, IV and V do spread to new strains and even to different species of staphylococci 6,38–40 . Replication could also help prevent loss of the element by providing more substrates for reintegration after excision.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcal SCCmec elements encode an active MCM-like helicase and thus may be replicative

Mir-Sanchis

Roman

Misiura

et al. 2016

Nat Struct Mol Biol

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Methicillin resistant Staphylococcus aureus (MRSA) is a public health threat worldwide. Although the mobile genomic island responsible for this phenotype, called SCC, was labeled non-replicative, we predicted DNA replication-related functions for some of their conserved proteins. We show that one of these, Cch, is homologous to the self-loading initiator helicases of an unrelated family of genomic islands, that it is an active 3’ to 5' helicase, and that the adjacent ORF encodes an ssDNA-binding protein. Our 2.9Å crystal structure of intact Cch shows that it forms a hexameric ring. Cch belongs to the pre-sensor II insert clade of AAA+ ATPases, as do the archaeal and eukaryotic MCM-family replicative helicases. Additionally, we find that SCC elements are part of a broader family of mobile elements that all encode a replication initiator upstream of their recombinases. Replication after excision would enhance the efficiency of horizontal gene transfer.

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Section: Discussionmentioning

confidence: 99%

Staphylococcal SCCmec elements encode an active MCM-like helicase and thus may be replicative

Mir-Sanchis

Roman

Misiura

et al. 2016

Nat Struct Mol Biol

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“…S. aureus has acquired resistance to practically all known antibiotics, necessitating the discovery of new therapeutic targets and the development of novel strategies to treat infections caused by this pathogen [ 5 , 21 , 22 ]. Surface-associated virulence factors, exotoxins, enterotoxins, and superantigens contribute to the pathogenicity of S. aureus [ 23 ]. Exotoxins from S. aureus , including α-toxin, β-toxin, δ-toxin, PVL, and Phenol-Soluble Modulins (PSMs), all contribute to the lysis of leukocytes [ 24 ], and α-toxin and PSMs may also contribute to the formation of biofilms [ 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

SaeR as a novel target for antivirulence therapy against Staphylococcus aureus

Gao,

Wei,

Hou

et al. 2023

Emerging Microbes & Infections

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Staphylococcus aureus is a major human pathogen responsible for a wide range of clinical infections. SaeRS is one of the two-component systems in S. aureus that modulate multiple virulence factors. Although SaeR is required for S. aureus to develop an infection, inhibitors have not been reported. Using an in vivo knockdown method, we demonstrated that SaeR is targetable for the discovery of antivirulence agent. HR3744 was discovered through a high-throughput screening utilizing a GFP-Lux dual reporter system driven by saeP1 promoter. The antivirulence efficacy of HR3744 was tested using Western blot, Quantitative Polymerase Chain Reaction, leucotoxicity, and haemolysis tests. In electrophoresis mobility shift assay, HR3744 inhibited SaeR-DNA probe binding. WaterLOGSY-NMR test showed HR3744 directly interacted with SaeR’s DNA-binding domain. When SaeR was deleted, HR3744 lost its antivirulence property, validating the target specificity. Virtual docking and mutagenesis were used to confirm the target’s specificity. When Glu159 was changed to Asn, the bacteria developed resistance to HR3744. A structure–activity relationship study revealed that a molecule with a slight modification did not inhibit SaeR, indicating the selectivity of HR3744. Interestingly, we found that SAV13, an analogue of HR3744, was four times more potent than HR3744 and demonstrated identical antivirulence properties and target specificity. In a mouse bacteraemia model, both HR3744 and SAV13 exhibited in vivo effectiveness. Collectively, we identified the first SaeR inhibitor, which exhibited in vitro and in vivo antivirulence properties, and proved that SaeR could be a novel target for developing antivirulence drugs against S. aureus infections.

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“…Hence, this is a worrisome situation given that these children still have poorly developed immune system and are not able to mount resistance as observed in adults. They thus need to be protected from the risks posed by these invasive organisms ( 19 , 20 ). In Abia State, \southeast Nigeria, higher prevalence of 50% nasal colonization in hospital and non-hospital subjects has been reported ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

The Prevalence and Risk Factors Associated with Nasal Methicillin- Resistant Staphylococcus Aureus Colonization among Children in a Tertiary Hospital in Nigeria

Tuta

Okesola

Umeokonkwo

1970

Ethiop J Health Sci

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BACKGROUND: Nasal methicillin-resistant Staphylococcus aureus (MRSA) colonization is of public health concern due to increased risk of developing invasive infections and the therapeutic challenges. This concern is more among the vulnerable group. We determined the prevalence and associated risk factors of MRSA nasal carriage among children in a tertiary hospital in Nigeria.METHOD: We conducted a hospital-based, cross-sectional study among 300 children attending the outpatient clinic of a tertiary hospital recruited through systematic sampling technique. An interviewer-administered, structured questionnaire was used to obtain sociodemographic characteristics and exposure factors. Nasal swabs samples were collected and inoculated on mannitol salt agar and subcultured on nutrient agar to isolate Staphylococcus aureus. We used the conventional Polymerase Chain Reaction (PCR) technique to detect the presence of mecA gene for MRSA. We calculated the prevalence, prevalence odds ratio to determine risk factors for MRSA acquisition at 5% level of significance.RESULTS: The median age was 1.7 years (6 months-16 years). Males accounted for 60.7%, and 75% of the participants were under 5 years. Staphylococcus aureus colonization was found in 36.3% of the participants while 5.3% of the participants had MRSA identified by detecting the mecA gene. History of recent surgery in the last six months was the only independent predictor of nasal MRSA colonization among the participants (aOR=12.5; 95%CI: 2.7-50.0.)CONCLUSION: The high prevalence of MRSA colonization observed among the children in this study suggests the need to consider screening children with history of previous surgery as infection control and prevention intervention for MRSA.

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Treatment of Staphylococcal Infections

Cited by 8 publications

References 211 publications

Staphylococcal SCCmec elements encode an active MCM-like helicase and thus may be replicative

Staphylococcal SCCmec elements encode an active MCM-like helicase and thus may be replicative

SaeR as a novel target for antivirulence therapy against Staphylococcus aureus

The Prevalence and Risk Factors Associated with Nasal Methicillin- Resistant Staphylococcus Aureus Colonization among Children in a Tertiary Hospital in Nigeria

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