Antimycobacterial Activities of Endolysins Derived From a Mycobacteriophage, BTCU-1

Lai, Ming-Kuen; Liu, Chih‐Chin; Jiang, Shinn‐Jong; Soo, Po-Chi; Tu, Meng-Hsuan; Lee, Jen-Jyh; Chen, Ying-Huei; Chang, Kai‐Chih

doi:10.3390/molecules201019277

Cited by 37 publications

(38 citation statements)

References 28 publications

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“…As a result, the mycolic acid layer detaches from the cell, rendering vulnerable to osmotic shock and, finally, lysis ( 155 ). Some in vitro assays have been conducted with both mycobacteriophage-derived hydrolases, yielding, in general, promising results that show either growth arrest ( 101 ) or a bactericidal effect ( 103 ), but further research is still required. The mycobacterial endolysins and their therapeutical potential have been recently reviewed ( 156 ).…”

Section: Lysins Against Gram-positive Bacteriamentioning

confidence: 99%

Phage Lysins for Fighting Bacterial Respiratory Infections: A New Generation of Antimicrobials

2018

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Lower respiratory tract infections and tuberculosis are responsible for the death of about 4.5 million people each year and are the main causes of mortality in children under 5 years of age. Streptococcus pneumoniae is the most common bacterial pathogen associated with severe pneumonia, although other Gram-positive and Gram-negative bacteria are involved in respiratory infections as well. The ability of these pathogens to persist and produce infection under the appropriate conditions is also associated with their capacity to form biofilms in the respiratory mucous membranes. Adding to the difficulty of treating biofilm-forming bacteria with antibiotics, many of these strains are becoming multidrug resistant, and thus the alternative therapeutics available for combating this kind of infections are rapidly depleting. Given these concerns, it is urgent to consider other unconventional strategies and, in this regard, phage lysins represent an attractive resource to circumvent some of the current issues in infection treatment. When added exogenously, lysins break specific bonds of the peptidoglycan and have potent bactericidal effects against susceptible bacteria. These enzymes possess interesting features, including that they do not trigger an adverse immune response and raise of resistance is very unlikely. Although Gram-negative bacteria had been considered refractory to these compounds, strategies to overcome this drawback have been developed recently. In this review we describe the most relevant in vitro and in vivo results obtained to date with lysins against bacterial respiratory pathogens.

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Section: Lysins Against Gram-positive Bacteriamentioning

confidence: 99%

Phage Lysins for Fighting Bacterial Respiratory Infections: A New Generation of Antimicrobials

2018

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“…Grover et al [186] reported that LysB isolated from the mycobacteriophage Bxz2 has 10-fold higher esterase activity than LysB isolated from the mycobacteriophage Ms6, but that both effectively inhibit the growth of M. smegmatis. Lai et al [187] showed that LysA and LysB isolated from the mycobacteriophage BTCU-1, besides being active against M. smegmatis when administered exogenously, thereby causing severe modifications on the cell wall structure, also inhibited the viability of this mycobacterium growing inside RAW 264.7 macrophages. The promising results of these studies prove that an endolysin approach to treating mycobacterial infections can be applied in the future, also in combination with conventional antibiotics that target the mycobacterial cell wall.…”

Section: Bacteriophagesmentioning

confidence: 99%

Looking beyond Typical Treatments for Atypical Mycobacteria

2020

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The genus Mycobacterium comprises not only the deadliest of bacterial pathogens, Mycobacterium tuberculosis, but several other pathogenic species, including M. avium and M. abscessus. The incidence of infections caused by atypical or nontuberculous mycobacteria (NTM) has been steadily increasing, and is associated with a panoply of diseases, including pulmonary, soft-tissue, or disseminated infections. The treatment for NTM disease is particularly challenging, due to its long duration, to variability in bacterial susceptibility profiles, and to the lack of evidence-based guidelines. Treatment usually consists of a combination of at least three drugs taken from months to years, often leading to severe secondary effects and a high chance of relapse. Therefore, new treatment approaches are clearly needed. In this review, we identify the main limitations of current treatments and discuss different alternatives that have been put forward in recent years, with an emphasis on less conventional therapeutics, such as antimicrobial peptides, bacteriophages, iron chelators, or host-directed therapies. We also review new forms of the use of old drugs, including the repurposing of non-antibacterial molecules and the incorporation of antimicrobials into ionic liquids. We aim to stimulate advancements in testing these therapies in relevant models, in order to provide clinicians and patients with useful new tools with which to treat these devastating diseases.

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“…(Hatfull, 2010). These phages, which are referred to as mycobacteriophages, can kill the bacteria during Recently, one such phage named BTCU-1 that specifically infects Mycobacterium was isolated from a soil sample in Taiwan (Lai et al, 2015). Images of the phage captured using TEM reveal that the phage resembles members of the Siphoviridae family.…”

Section: Introductionmentioning

confidence: 99%

Expression, purification and crystallization of phosphoribosyl transferase from a mycobacteriophage

Lei¹,

Lee²,

Shaw³

2018

Acta Cryst Sect F

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Tuberculosis (TB) continues to remain a leading cause of death globally. Of particular concern is the emergence and rise in incidence of multidrug-resistant and extremely drug-resistant cases of TB. To counter this threat, it is important to explore alternative therapies, including phage therapy. Phage BTCU-1 specifically infects Mycobacterium spp. and kills the majority of them. Intriguingly, many proteins from the phage do not share high amino-acid sequence identity with proteins from species other than phages. Here, the expression, purification and crystallization of one such protein, a putative phosphoribosyl transferase from phage BTCU-1, is reported. The crystals belonged to space group C222, with unit-cell parameters a = 59.71, b = 64.42, c = 65.32 Å, α = β = γ = 90°. The crystals diffracted X-rays to 2.2 Å resolution.

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Antimycobacterial Activities of Endolysins Derived From a Mycobacteriophage, BTCU-1

Cited by 37 publications

References 28 publications

Phage Lysins for Fighting Bacterial Respiratory Infections: A New Generation of Antimicrobials

Phage Lysins for Fighting Bacterial Respiratory Infections: A New Generation of Antimicrobials

Looking beyond Typical Treatments for Atypical Mycobacteria

Expression, purification and crystallization of phosphoribosyl transferase from a mycobacteriophage

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