Antimicrobial activity of LysSS, a novel phage endolysin, against Acinetobacter baumannii and Pseudomonas aeruginosa

Kim, Shukho; Lee, Da-Won; Jin, Jong Sook; Kim, Jungmin

doi:10.1016/j.jgar.2020.01.005

Cited by 91 publications

(82 citation statements)

References 31 publications

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“…Several natural known endolysins also exhibited antibacterial activity against Gram-negative bacteria in the absence of OMPs, such as OBPgp279 against P. aeruginosa, PlyF307 and LysAB21 against A. baumannii (Lai et al, 2011;Walmagh et al, 2012;Lood et al, 2015). It is demonstrated with increasing evidence that several endolysins are active against multiple Gram-negative bacteria, and few of them are reported active against Gram-positive pathogens in vitro, such as Abtn-4 (Yuan et al, 2020), LysSAP26 (Kim et al, 2020a), and LysSS (Kim et al, 2020b). Such lysins with broad host-range are commonly contain a lysozyme or glycoside hydrolase catalytic activity, which cleaves the b-1,4-glycosidic linkage between N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) in peptidoglycans that is generally shared by various bacteria (Ghose and Euler, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…However, treatment bacteria with outer membrane permeabilizers (OMPs), such as citric acid, trichloroethane (CHCl 3 ), Triton X-100, and EDTA, can improve the antibacterial activity of endolysins and conquer the hindrance presented by the outer membrane of Gram-negative bacteria (Helander and Mattila-Sandholm, 2000;Briers et al, 2007;Briers et al, 2011;Briers et al, 2014;Yang et al, 2015b;Guo et al, 2017). In this context, several endolysins have showed improved or synergistic bactericidal activity against MDR A. baumannii and P. aeruginosa in the presence of OMPs, including LysSS (Kim et al, 2020b), Abtn-4 (Yuan et al, 2020), LysPA26 (Guo et al, 2017), PlyA (Yang et al, 2015b), ABgp46 (Oliveira et al, 2016), and OBPgp279 (Walmagh et al, 2012). However, lysins with OMP-independent antibacterial activity against Gram-negative microbes still un-adequately addressed since few of them are demonstrated effective in animal infection models.…”

Section: Introductionmentioning

confidence: 99%

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A Novel Acinetobacter baumannii Bacteriophage Endolysin LysAB54 With High Antibacterial Activity Against Multiple Gram-Negative Microbes

Khan

Gondil

et al. 2021

Front. Cell. Infect. Microbiol.

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The rapid spread and emergence of multidrug-resistant Acinetobacter baumannii and other pathogenic Gram-negative bacteria spurred scientists and clinicians to look for alternative therapeutic agents to conventional antibiotics. In the present study, an A. baumannii bacteriophage p54 was isolated and characterized. Morphological and genome analysis revealed that bacteriophage p54 belongs to Myoviridae family with a genome size of 165,813 bps. A novel endolysin, namely LysAB54, showing low similarity with other well-known related endolysins, was cloned, expressed, and characterized from the bacteriophage p54. LysAB54 showed significant bactericidal activity against multidrug-resistant A. baumannii and other Gram-negative bacteria, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli, in the absence of outer membrane permeabilizers. Based on all those observations, LysAB54 could represent a potential agent for the treatment of multidrug-resistant Gram-negative superbugs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Novel Acinetobacter baumannii Bacteriophage Endolysin LysAB54 With High Antibacterial Activity Against Multiple Gram-Negative Microbes

Khan

Gondil

et al. 2021

Front. Cell. Infect. Microbiol.

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“…The chances of bacteria developing resistance toward endolysins are low since endolysins target cell wall molecules essential for bacterial viability ( Łusiak-Szelachowska et al, 2020 ). Phage-derived endolysins are promising candidates for treating secondary bacterial infections or multi-drug resistant infections ( Imanishi et al, 2019 ; Kim et al, 2020 ). There are five main classes of endolysins based on their enzymatic specificity ( Figure 4 ) ( Schmelcher et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Secondary Bacterial Infections During Pulmonary Viral Disease: Phage Therapeutics as Alternatives to Antibiotics?

et al. 2020

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Secondary bacterial infections manifest during or after a viral infection(s) and can lead to negative outcomes and sometimes fatal clinical complications. Research and development of clinical interventions is largely focused on the primary pathogen, with research on any secondary infection(s) being neglected. Here we highlight the impact of secondary bacterial infections and in particular those caused by antibiotic-resistant strains, on disease outcomes. We describe possible non-antibiotic treatment options, when small molecule drugs have no effect on the bacterial pathogen and explore the potential of phage therapy and phage-derived therapeutic proteins and strategies in treating secondary bacterial infections, including their application in combination with chemical antibiotics.

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“…In the case of Gram-negative bacteria, the peptidoglycan layer is shielded by an outer membrane (OM). Nonetheless, some natural lysins were reported to have limited antibacterial activity when applied extracellularly (Morita et al 2001;Lai et al 2011;Wu et al 2019;Kim et al 2020). Orito and co-workers hypothesized this effect is related to the presence of an amphipathic C-terminal region that is responsible for a local OM permeabilization, granting access to the peptidoglycan layer (Orito et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Advanced engineering of third-generation lysins and formulation strategies for clinical applications

Maesschalck

Gutiérrez

Paeshuyse

et al. 2020

Critical Reviews in Microbiology

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One of the possible solutions for the current antibiotic resistance crisis may be found in (often bacteriophage-derived) peptidoglycan hydrolases. The first clinical trials of these natural enzymes, coined here as first-generation lysins, are currently ongoing. Moving beyond natural endolysins with protein engineering established the second generation of lysins. In second-generation lysins, the focus lies on improving antibacterial and biochemical properties such as antimicrobial activity and stability, as well as expanding their activities towards Gram-negative pathogens. However, solutions to particular key challenges regarding clinical applications are only beginning to emerge in the third generation of lysins, in which protein and biochemical engineering efforts focus on improving properties relevant under clinical conditions. In addition, increasingly advanced formulation strategies are developed to increase the bioavailability, antibacterial activity, and half-life, and to reduce pro-inflammatory responses. This review focuses on third-generation and advanced formulation strategies that are developed to treat infections, ranging from topical to systemic applications. Together, these efforts may fully unlock the potential of lysin therapy and will propel it as a true antibiotic alternative or supplement.

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Antimicrobial activity of LysSS, a novel phage endolysin, against Acinetobacter baumannii and Pseudomonas aeruginosa

Cited by 91 publications

References 31 publications

A Novel Acinetobacter baumannii Bacteriophage Endolysin LysAB54 With High Antibacterial Activity Against Multiple Gram-Negative Microbes

A Novel Acinetobacter baumannii Bacteriophage Endolysin LysAB54 With High Antibacterial Activity Against Multiple Gram-Negative Microbes

Secondary Bacterial Infections During Pulmonary Viral Disease: Phage Therapeutics as Alternatives to Antibiotics?

Advanced engineering of third-generation lysins and formulation strategies for clinical applications

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