Teicoplanin resistance in Staphylococcus haemolyticus is associated with mutations in histidine kinases VraS and WalK

Vimberg, Vladimir; Cavanagh, Jorunn Pauline; Benada, Oldřich; Kofroňová, Olga; Hjerde, Erik; Zieglerová, Leona; Novotná, Gabriela Balíková

doi:10.1016/j.diagmicrobio.2017.11.007

Cited by 9 publications

(5 citation statements)

References 41 publications

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“…In brief, the most common glycopeptide antibiotic resistance in enterococci is due to cell wall reprogramming by enzymes encoded in vanHAX gene clusters that produce peptidoglycan precursors containing either D-alanine-D-lactate (D-Ala-D-Lac) or D-alanine-D-serine instead of the dipeptide D-alanine-D-alanine (D-Ala-D-Ala), decreasing the affinity of glycopeptide antibiotics to the peptidoglycan (see Figure 4A). In staphylococci, glycopeptide antibiotic resistance is developed mostly by a series of subsequent mutations in genes involved in cell wall metabolism and stress response, linking the resistance phenotype to cell wall thickening, the misregulation of autolysis, and changes in the cell surface anionic charges; this altogether shelters the cell wall synthesis machinery, which is located in the septum of the cells, from the inhibitory action of antibiotics (see Figure 4B) [10,42]. Resistance to teicoplanin in S. aureus (>2 µg/mL minimal inhibitory concentration (MIC)) and coagulase-negative staphylococci (CoNS) (>4 µg/mL) were associated with poor clinical prognosis in patients (reviewed by Blaskovich et al, 2018) [41].…”

Section: Threats To Be Considered In Teicoplanin Usagementioning

confidence: 99%

Teicoplanin—A New Use for an Old Drug in the COVID-19 Era?

Vimberg

2021

Pharmaceuticals

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Teicoplanin is an antibiotic that has been actively used in medical practice since 1986 to treat serious Gram-positive bacterial infections. Due to its efficiency and low cytotoxicity, teicoplanin has also been used for patients with complications, including pediatric and immunocompromised patients. Although teicoplanin is accepted as an antibacterial drug, its action against RNA viruses, including SARS-CoV2, has been proven in vitro. Here, we provide a thorough overview of teicoplanin usage in medicine, based on the current literature. We summarize infection sites treated with teicoplanin, concentrations of the antibiotic in different organs, and side effects. Finally, we summarize all available data about the antiviral activity of teicoplanin. We believe that, due to the extensive experience of teicoplanin usage in clinical settings to treat bacterial infections and its demonstrated activity against SARS-CoV2, teicoplanin could become a drug of choice in the treatment of COVID-19 patients. Teicoplanin stops the replication of the virus and at the same time avoids the development of Gram-positive bacterial co-infections.

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Section: Threats To Be Considered In Teicoplanin Usagementioning

confidence: 99%

Teicoplanin—A New Use for an Old Drug in the COVID-19 Era?

Vimberg

2021

Pharmaceuticals

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“…28,29 However, only one mutation in VraS (Q289K) has been directly shown to confer teicoplanin resistance. 28 Inactivation of the 3-cistronic transcript comprising tcaR-tcaA-tcaB increases resistance of staphylococci to teicoplanin but not to vancomycin. 30 TcaB is a membrane protein with 11 transmembrane domains (Figure 3) and shows homology with the MFS multidrug transporter of the Bcr/CflA family; however, its exact function has not been studied.…”

Section: Vancomycin and Teicoplaninmentioning

confidence: 99%

“…Several resistance mechanisms are specific to teicoplanin. For example, mutations in both VraT and VraS are commonly associated with higher resistance to teicoplanin 28,29 . However, only one mutation in VraS (Q289K) has been directly shown to confer teicoplanin resistance 28 .…”

Section: Vancomycin and Teicoplaninmentioning

confidence: 99%

“…For example, mutations in both VraT and VraS are commonly associated with higher resistance to teicoplanin 28,29 . However, only one mutation in VraS (Q289K) has been directly shown to confer teicoplanin resistance 28 . Inactivation of the 3‐cistronic transcript comprising tcaR‐tcaA‐tcaB increases resistance of staphylococci to teicoplanin but not to vancomycin 30 .…”

Section: Vancomycin and Teicoplaninmentioning

confidence: 99%

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Role of membrane proteins in bacterial resistance to antimicrobial peptides

Vimberg

Buriánková

Mazumdar

et al. 2021

Medicinal Research Reviews

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Several natural antimicrobial peptides (AMPs), including the novel semisynthetic lipoglycopeptide antibiotics telavancin, dalbavancin, and oritavancin, have been approved for clinical use to address the growing problem of multiple antibioticresistant Gram-positive bacterial infections. Nevertheless, the efficacy of these antibiotics has already been compromised. The SARS-CoV-2 pandemic led to the increased clinical use of all antibiotics, further promoting the development of bacterial resistance. Therefore, it is critical to gain a deeper understanding of the role of resistance mechanisms to minimize the consequential risks of long-term antibiotic use and misuse.Here, we summarize for the first time the current knowledge of resistance mechanisms that have been shown to cause resistance to clinically used AMPs, with particular focus on membrane proteins that have been reported to interfere with the activity of AMPs by affecting the binding of AMPs to bacteria.

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“…Open Access mutations in S. aureus lead to drug-resistant [4] whereas mutations in lysostaphin lead to the dysfunction of lysostaphin. Indeed, previous studies have suggested that the site-directed mutants in lysostaphin can abolish its killing activity, i.e.…”

Section: Introductionmentioning

confidence: 99%

Mutation Patterns in Lysostaphin

Zhang¹,

Ye²,

Yan³

et al. 2019

JBiSE

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Lysostaphin is widely used in clinical settings against Staphylococcus aureus, but its mutants can abolish its killing activity. The difficulty in studies of mutations in lysostaphin is the shortage of data, which may need many decades to collect, although lysostaphin is so important for clinical therapeutics and drug development. In order not to passively wait for the accumulation of new data, in this study 1) the 23,442 mutations in 1408 proteins from databank were used to determine whether the mutations in lysostaphin follow the general mutation trend obtained from the databank, 2) the amino-acid pair predictability was used to explore the underlined mechanism for lysostaphin mutations, and 3) the amino-acid distribution probability was used to associate the mutation with dysfunction of lysostaphin. The results show that the mutations in lysostaphin follow the general trend of mutations in proteins; the underlined mechanism for mutations in lysostaphin is explainable from a viewpoint of randomness, and a mutation with increased distribution probability would have a larger chance to dysfunction lysostaphin. This study provides useful information for future design of anti-S. aureus drug and enzyme engineering.

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Teicoplanin resistance in Staphylococcus haemolyticus is associated with mutations in histidine kinases VraS and WalK

Cited by 9 publications

References 41 publications

Teicoplanin—A New Use for an Old Drug in the COVID-19 Era?

Teicoplanin—A New Use for an Old Drug in the COVID-19 Era?

Role of membrane proteins in bacterial resistance to antimicrobial peptides

Mutation Patterns in Lysostaphin

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