Lipophosphonoxins II: Design, Synthesis, and Properties of Novel Broad Spectrum Antibacterial Agents

Seydlová, Gabriela; Pohl, Radek; Zborníková, Eva; Ehn, Marcel; Šimák, Ondřej; Panova, Natalya; Kolář, Milan; Bogdanová, Kateřina; Večeřová, Renata; Fišer, Radovan; Šanderová, Hana; Vítovská, Dragana; Sudzinová, Petra; Pospíšil, Jiří; Benada, Oldřich; Křížek, Tomáš; Sedlák, David; Bartůněk, Petr; Krásný, Libor; Rejman, Dominik

doi:10.1021/acs.jmedchem.7b00355

Cited by 29 publications

(44 citation statements)

References 35 publications

(56 reference statements)

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“…Kovalchuk et al (2007) showed that a complex of natural cytokines and AMPs (CCAP or Superlymph) inhibits virus proliferation in vitro. Therefore, due to their small molecular weight, good thermal stability and broad antimicrobial spectrum, AMPs are expected to replace antibiotics as new and highly effective antibacterial drugs (Presicce et al 2009;Seydlová et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Antifungal Activity and Physicochemical Properties of a Novel Antimicrobial Protein AMP-17 from Musca domestica

Yang

Guo

Zhao

et al. 2019

Polish Journal of Microbiology

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Antimicrobial peptides (AMPs) are cationic small peptide chains that have good antimicrobial activity against a variety of bacteria, fungi, and viruses. AMP-17 is a recombinant insect AMP obtained by a prokaryotic expression system. However, the full antifungal activity, physicochemical characteristics, and cytotoxicity of AMP-17 were previously unknown. AMP-17 was shown to have good antifungal activity against five pathogenic fungi, with minimum inhibitory concentrations (MIC) of 9.375–18.75 μg/ml, and minimum fungicidal concentrations (MFC) of 18.75–37.5 μg/ml. Notably, the antifungal activity of AMP-17 against Cryptococcus neoformans was superior to that of other Candida spp. In addition, the hemolytic rate of AMP-17 was only 1.47%, even at the high concentration of 16 × MIC. AMP-17 was insensitive to temperature and high salt ion concentration, with temperatures of 98°C and –80°C, and NaCl and MgCl2 concentrations of 50–200 mmol/l, having no significant effect on antifungal activity. However, AMP-17 was sensitive to proteases, trypsin, pepsin, and proteinase K. The elucidation of antifungal activity, physicochemical properties and cytotoxicity of AMP-17 provided an experimental basis for its safety evaluation and application, as well as indicated that AMP-17 might be a promising drug.

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Section: Introductionmentioning

confidence: 99%

Antifungal Activity and Physicochemical Properties of a Novel Antimicrobial Protein AMP-17 from Musca domestica

Yang

Guo

Zhao

et al. 2019

Polish Journal of Microbiology

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“…coli polar lipid extract (Avanti Polar Lipids, Alabaster, AL, USA), or soybean lipids (Asolectin-Type II, Merck KGaA, Darmstadt, Germany). Experiments were performed as described previously 50 . The effect of colZ on peptidoglycan was tested using the dye release method described in Zhou et al .…”

Section: Methodsmentioning

confidence: 99%

Colicin Z, a structurally and functionally novel colicin type that selectively kills enteroinvasive Escherichia coli and Shigella strains

Micenková

Bosák

Kučera

et al. 2019

Sci Rep

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Colicin production in Escherichia coli ( E . coli ) strains represents an important trait with regard to microbial survival and competition in the complex intestinal environment. A novel colicin type, colicin Z (26.3 kDa), was described as a product of an original producer, extraintestinal E . coli B1356 strain, isolated from the anorectal abscess of a 17 years-old man. The 4,007 bp plasmid (pColZ) was completely sequenced and colicin Z activity ( cza ) and colicin Z immunity ( czi ) genes were identified. The cza and czi genes are transcribed in opposite directions and encode for 237 and 151 amino acid-long proteins, respectively. Colicin Z shows a narrow inhibitory spectrum, being active only against enteroinvasive E . coli (EIEC) and Shigella strains via CjrC receptor recognition and CjrB- and ExbB-, ExbD-mediated colicin translocation. All tested EIEC and Shigella strains isolated between the years 1958–2010 were sensitive to colicin Z. The lethal effect of colicin Z was found to be directed against cell wall peptidoglycan (PG) resulting in PG degradation, as revealed by experiments with Remazol Brilliant Blue-stained purified peptidoglycans and with MALDI-TOF MS analyses of treated PG. Colicin Z represents a new class of colicins that is structurally and functionally distinct from previously studied colicin types.

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“…Black lipid membrane measurements. Planar lipid membrane experiments were performed as described previously (62,63).…”

Section: Methodsmentioning

confidence: 99%

Colicin U from Shigella boydii Forms Voltage-Dependent Pores

et al. 2019

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Colicin U is a protein produced by the bacterium Shigella boydii (serovars 1 and 8). It exerts antibacterial activity against strains of the enterobacterial genera Shigella and Escherichia. Here, we report that colicin U forms voltage-dependent pores in planar lipid membranes; its single-pore conductance was found to be about 22 pS in 1 M KCl at pH 6 under 80 mV in asolectin bilayers. In agreement with the high degree of homology between their C-terminal domains, colicin U shares some pore characteristics with the related colicins A and B. Colicin U pores are strongly pH dependent, and as we deduced from the activity of colicin U in planar membranes at different protein concentrations, they have a monomeric pore structure. However, in contrast to related colicins, we observed a very low cationic selectivity of colicin U pores (1.5/1 of K+/Cl− at pH 6) along with their atypical voltage gating. Finally, using nonelectrolytes, we determined the inner diameter of the pores to be in the range of 0.7 to 1 nm, which is similar to colicin Ia, but with a considerably different inner profile. IMPORTANCE Currently, a dramatic increase in antibiotic resistance is driving researchers to find new antimicrobial agents. The large group of toxins called bacteriocins appears to be very promising from this point of view, especially because their narrow killing spectrum allows specific targeting against selected bacterial strains. Colicins are a subgroup of bacteriocins that act on Gram-negative bacteria. To date, some colicins are commercially used for the treatment of animals (1) and tested as a component of engineered species-specific antimicrobial peptides, which are studied for the potential treatment of humans (2). Here, we present a thorough single-molecule study of colicin U which leads to a better understanding of its mode of action. It extends the range of characterized colicins available for possible future medical applications.

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Lipophosphonoxins II: Design, Synthesis, and Properties of Novel Broad Spectrum Antibacterial Agents

Cited by 29 publications

References 35 publications

Antifungal Activity and Physicochemical Properties of a Novel Antimicrobial Protein AMP-17 from Musca domestica

Antifungal Activity and Physicochemical Properties of a Novel Antimicrobial Protein AMP-17 from Musca domestica

Colicin Z, a structurally and functionally novel colicin type that selectively kills enteroinvasive Escherichia coli and Shigella strains

Colicin U from Shigella boydii Forms Voltage-Dependent Pores

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