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Snake Cathelicidin NA-CATH and Smaller Helical Antimicrobial Peptides Are Effective against Burkholderia thailandensis.

Blower RJ, Barksdale SM, van Hoek ML - PLoS Negl Trop Dis (2015)

Bottom Line: The D-enantiomer of one small peptide (ATRA-1A) was found to be antimicrobial as well, with EC50 in the range of the L-enantiomer.We also found that the cathelicidin peptides, including LL-37, NA-CATH, and SMAP-29, possessed significant ability to prevent biofilm formation of B. thailandensis.These results demonstrate that although B. thailandensis is highly resistant to many antibiotics, cyclic peptide antibiotics such as polymyxin B, and defensing peptides, some antimicrobial peptides including the elapid snake cathelicidin NA-CATH exert significant antimicrobial and antibiofilm activity towards B. thailandensis.

View Article: PubMed Central - PubMed

Affiliation: George Mason University, School of Systems Biology, Manassas, Virginia, United States of America.

ABSTRACT
Burkholderia thailandensis is a Gram-negative soil bacterium used as a model organism for B. pseudomallei, the causative agent of melioidosis and an organism classified category B priority pathogen and a Tier 1 select agent for its potential use as a biological weapon. Burkholderia species are reportedly "highly resistant" to antimicrobial agents, including cyclic peptide antibiotics, due to multiple resistance systems, a hypothesis we decided to test using antimicrobial (host defense) peptides. In this study, a number of cationic antimicrobial peptides (CAMPs) were tested in vitro against B. thailandensis for both antimicrobial activity and inhibition of biofilm formation. Here, we report that the Chinese cobra (Naja atra) cathelicidin NA-CATH was significantly antimicrobial against B. thailandensis. Additional cathelicidins, including the human cathelicidin LL-37, a sheep cathelicidin SMAP-29, and some smaller ATRA peptide derivatives of NA-CATH were also effective. The D-enantiomer of one small peptide (ATRA-1A) was found to be antimicrobial as well, with EC50 in the range of the L-enantiomer. Our results also demonstrate that human alpha-defensins (HNP-1 & -2) and a short beta-defensin-derived peptide (Peptide 4 of hBD-3) were not bactericidal against B. thailandensis. We also found that the cathelicidin peptides, including LL-37, NA-CATH, and SMAP-29, possessed significant ability to prevent biofilm formation of B. thailandensis. Additionally, we show that LL-37 and its D-enantiomer D-LL-37 can disperse pre-formed biofilms. These results demonstrate that although B. thailandensis is highly resistant to many antibiotics, cyclic peptide antibiotics such as polymyxin B, and defensing peptides, some antimicrobial peptides including the elapid snake cathelicidin NA-CATH exert significant antimicrobial and antibiofilm activity towards B. thailandensis.

No MeSH data available.


Related in: MedlinePlus

Antimicrobial activity of NA-CATH derivatives against B thailandensis.B. thailandensis was incubated for 3 h with various peptide concentrations in 10 mM sodium phosphate buffer (pH 7.4); percent (%) survival was calculated as the ratio of CFUs before and after incubation. (A) EC50 of ATRA-1 and ATRA-1A. (B)ATRA-2 did not exhibit antimicrobial activity.
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pntd.0003862.g002: Antimicrobial activity of NA-CATH derivatives against B thailandensis.B. thailandensis was incubated for 3 h with various peptide concentrations in 10 mM sodium phosphate buffer (pH 7.4); percent (%) survival was calculated as the ratio of CFUs before and after incubation. (A) EC50 of ATRA-1 and ATRA-1A. (B)ATRA-2 did not exhibit antimicrobial activity.

Mentions: Naja atra cathelicidin peptide derivatives were tested for antimicrobial activity against B. thailandensis. Each imperfect repeat from NA-CATH (ATRA-1 and ATRA-2) was tested, as well as the synthetic peptide ATRA-1A, in which amino acid 3 of ATRA-1 was switched from phenylalanine to alanine [13] [26]. The EC50 of ATRA-1 against B. thailandensis was determined to be 6.94 μM (95% CI of 4.26–11.3 μM) (Fig 2). EC50 plating assays determined that ATRA-2 was not an effective antimicrobial peptide, correlating with our previous ATRA-2 results with other bacteria [14–16]. This leads to the conclusion that the first imperfect repeat of NA-CATH contributes to most of the observed antimicrobial activity of NA-CATH. We then looked at a synthetic peptide, named ATRA-1A, which contains a single amino acid change at position 3 (F->A). This synthetic peptide exhibited an EC50 of 9.83 μM (95% CI of 6.52–14.8 μM).


Snake Cathelicidin NA-CATH and Smaller Helical Antimicrobial Peptides Are Effective against Burkholderia thailandensis.

Blower RJ, Barksdale SM, van Hoek ML - PLoS Negl Trop Dis (2015)

Antimicrobial activity of NA-CATH derivatives against B thailandensis.B. thailandensis was incubated for 3 h with various peptide concentrations in 10 mM sodium phosphate buffer (pH 7.4); percent (%) survival was calculated as the ratio of CFUs before and after incubation. (A) EC50 of ATRA-1 and ATRA-1A. (B)ATRA-2 did not exhibit antimicrobial activity.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4510350&req=5

pntd.0003862.g002: Antimicrobial activity of NA-CATH derivatives against B thailandensis.B. thailandensis was incubated for 3 h with various peptide concentrations in 10 mM sodium phosphate buffer (pH 7.4); percent (%) survival was calculated as the ratio of CFUs before and after incubation. (A) EC50 of ATRA-1 and ATRA-1A. (B)ATRA-2 did not exhibit antimicrobial activity.
Mentions: Naja atra cathelicidin peptide derivatives were tested for antimicrobial activity against B. thailandensis. Each imperfect repeat from NA-CATH (ATRA-1 and ATRA-2) was tested, as well as the synthetic peptide ATRA-1A, in which amino acid 3 of ATRA-1 was switched from phenylalanine to alanine [13] [26]. The EC50 of ATRA-1 against B. thailandensis was determined to be 6.94 μM (95% CI of 4.26–11.3 μM) (Fig 2). EC50 plating assays determined that ATRA-2 was not an effective antimicrobial peptide, correlating with our previous ATRA-2 results with other bacteria [14–16]. This leads to the conclusion that the first imperfect repeat of NA-CATH contributes to most of the observed antimicrobial activity of NA-CATH. We then looked at a synthetic peptide, named ATRA-1A, which contains a single amino acid change at position 3 (F->A). This synthetic peptide exhibited an EC50 of 9.83 μM (95% CI of 6.52–14.8 μM).

Bottom Line: The D-enantiomer of one small peptide (ATRA-1A) was found to be antimicrobial as well, with EC50 in the range of the L-enantiomer.We also found that the cathelicidin peptides, including LL-37, NA-CATH, and SMAP-29, possessed significant ability to prevent biofilm formation of B. thailandensis.These results demonstrate that although B. thailandensis is highly resistant to many antibiotics, cyclic peptide antibiotics such as polymyxin B, and defensing peptides, some antimicrobial peptides including the elapid snake cathelicidin NA-CATH exert significant antimicrobial and antibiofilm activity towards B. thailandensis.

View Article: PubMed Central - PubMed

Affiliation: George Mason University, School of Systems Biology, Manassas, Virginia, United States of America.

ABSTRACT
Burkholderia thailandensis is a Gram-negative soil bacterium used as a model organism for B. pseudomallei, the causative agent of melioidosis and an organism classified category B priority pathogen and a Tier 1 select agent for its potential use as a biological weapon. Burkholderia species are reportedly "highly resistant" to antimicrobial agents, including cyclic peptide antibiotics, due to multiple resistance systems, a hypothesis we decided to test using antimicrobial (host defense) peptides. In this study, a number of cationic antimicrobial peptides (CAMPs) were tested in vitro against B. thailandensis for both antimicrobial activity and inhibition of biofilm formation. Here, we report that the Chinese cobra (Naja atra) cathelicidin NA-CATH was significantly antimicrobial against B. thailandensis. Additional cathelicidins, including the human cathelicidin LL-37, a sheep cathelicidin SMAP-29, and some smaller ATRA peptide derivatives of NA-CATH were also effective. The D-enantiomer of one small peptide (ATRA-1A) was found to be antimicrobial as well, with EC50 in the range of the L-enantiomer. Our results also demonstrate that human alpha-defensins (HNP-1 & -2) and a short beta-defensin-derived peptide (Peptide 4 of hBD-3) were not bactericidal against B. thailandensis. We also found that the cathelicidin peptides, including LL-37, NA-CATH, and SMAP-29, possessed significant ability to prevent biofilm formation of B. thailandensis. Additionally, we show that LL-37 and its D-enantiomer D-LL-37 can disperse pre-formed biofilms. These results demonstrate that although B. thailandensis is highly resistant to many antibiotics, cyclic peptide antibiotics such as polymyxin B, and defensing peptides, some antimicrobial peptides including the elapid snake cathelicidin NA-CATH exert significant antimicrobial and antibiofilm activity towards B. thailandensis.

No MeSH data available.


Related in: MedlinePlus