Effect of mutations in extracellular nuclease on the characteristics of the pigmented and nonpigmented Serratia marcescens strains

Nizamutdinova, E. Kh.; Shirshikova, Tatiana V.; Марданова, А. М.; Шарипова, М. Р.; Bogomolnaya, Lydia M.

doi:10.1134/s0026261716010069

Cited by 2 publications

(2 citation statements)

References 18 publications

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“…Given that peroxide exposure activates the macAB promoter ( Fig. 5F ), we evaluated the growth of wild type and Δ macAB mutant strains in LB broth supplemented with 10 mM H 2 O 2 ( 39 ). In the absence of H 2 O 2 , the Δ macAB mutant strain grew similarly to the wild-type strain ( Fig.…”

Section: Resultsmentioning

confidence: 99%

The ABC-Type Efflux Pump MacAB Is Involved in Protection of Serratia marcescens against Aminoglycoside Antibiotics, Polymyxins, and Oxidative Stress

Shirshikova

Sierra-Bakhshi

Kamaletdinova

et al. 2021

mSphere

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Serratia marcescens is an emerging pathogen with increasing clinical importance due to its intrinsic resistance to several classes of antibiotics. The chromosomally encoded drug efflux pumps contribute to antibiotic resistance and represent a major challenge for the treatment of bacterial infections. The ABC-type efflux pump MacAB was previously linked to macrolide resistance in Escherichia coli and Salmonella enterica serovar Typhimurium. The role of the MacAB homolog in antibiotic resistance of S. marcescens is currently unknown. We found that an S. marcescens mutant lacking the MacAB pump did not show increased sensitivity to the macrolide antibiotic erythromycin but was significantly more sensitive to aminoglycoside antibiotics and polymyxins. We also showed that, in addition to its role in drug efflux, the MacAB efflux pump is required for swimming motility and biofilm formation. We propose that the motility defect of the ΔmacAB mutant is due, at least in part, to the loss of functional flagella on the bacterial surface. Furthermore, we found that the promoter of the MacAB efflux pump was active during the initial hours of growth in laboratory medium and that its activity was further elevated in the presence of hydrogen peroxide. Finally, we demonstrate a complete loss of ΔmacAB mutant viability in the presence of peroxide, which is fully restored by complementation. Thus, the S. marcescens MacAB efflux pump is essential for survival during oxidative stress and is involved in protection from polymyxins and aminoglycoside antibiotics. IMPORTANCE The opportunistic pathogen Serratia marcescens can cause urinary tract infections, respiratory infections, meningitis, and sepsis in immunocompromised individuals. These infections are challenging to treat due to the intrinsic resistance of S. marcescens to an extensive array of antibiotics. Efflux pumps play a crucial role in protection of bacteria from antimicrobials. The MacAB efflux pump, previously linked to efflux of macrolides in Escherichia coli and protection from oxidative stress in Salmonella enterica serovar Typhimurium, is not characterized in S. marcescens. We show the role of the MacAB efflux pump in S. marcescens protection from aminoglycoside antibiotics and polymyxins, modulation of bacterial motility, and biofilm formation, and we illustrate the essential role for this pump in bacterial survival during oxidative stress. Our findings make the MacAB efflux pump an attractive target for inhibition to gain control over S. marcescens infections.

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Section: Resultsmentioning

confidence: 99%

The ABC-Type Efflux Pump MacAB Is Involved in Protection of Serratia marcescens against Aminoglycoside Antibiotics, Polymyxins, and Oxidative Stress

Shirshikova

Sierra-Bakhshi

Kamaletdinova

et al. 2021

mSphere

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“…Nonetheless, not all enzymes are alike. For example, Serratia marcescens nuclease (SMN), the activity of which requires magnesium ion (Mg 2+ ) [ 37 ], is extremely toxic to host cells [ 38 ]. Therefore, SMN is not an ideal candidate for CTVI.…”

Section: Mechanisms Of Ctvimentioning

confidence: 99%

Capsid-Targeted Viral Inactivation: A Novel Tactic for Inhibiting Replication in Viral Infections

Zhang

Jia

Zhou

et al. 2016

Viruses

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Capsid-targeted viral inactivation (CTVI), a conceptually powerful new antiviral strategy, is attracting increasing attention from researchers. Specifically, this strategy is based on fusion between the capsid protein of a virus and a crucial effector molecule, such as a nuclease (e.g., staphylococcal nuclease, Barrase, RNase HI), lipase, protease, or single-chain antibody (scAb). In general, capsid proteins have a major role in viral integration and assembly, and the effector molecule used in CTVI functions to degrade viral DNA/RNA or interfere with proper folding of viral key proteins, thereby affecting the infectivity of progeny viruses. Interestingly, such a capsid–enzyme fusion protein is incorporated into virions during packaging. CTVI is more efficient compared to other antiviral methods, and this approach is promising for antiviral prophylaxis and therapy. This review summarizes the mechanism and utility of CTVI and provides some successful applications of this strategy, with the ultimate goal of widely implementing CTVI in antiviral research.

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Effect of mutations in extracellular nuclease on the characteristics of the pigmented and nonpigmented Serratia marcescens strains

Cited by 2 publications

References 18 publications

The ABC-Type Efflux Pump MacAB Is Involved in Protection of Serratia marcescens against Aminoglycoside Antibiotics, Polymyxins, and Oxidative Stress

The ABC-Type Efflux Pump MacAB Is Involved in Protection of Serratia marcescens against Aminoglycoside Antibiotics, Polymyxins, and Oxidative Stress

Capsid-Targeted Viral Inactivation: A Novel Tactic for Inhibiting Replication in Viral Infections

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