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Leveraging family-specific signatures for AMP discovery and high-throughput annotation.

Waghu FH, Barai RS, Idicula-Thomas S - Sci Rep (2016)

Bottom Line: As compared to conventional antibiotics, AMPs exhibit broad spectrum antimicrobial activity, reduced toxicity and reduced microbial resistance.The webserver is available online at www.campsign.bicnirrh.res.in.In this work, we demonstrate an optimised and experimentally validated protocol along with a freely available webserver that uses family-based sequence signatures for accelerated discovery of novel AMPs.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Informatics Centre of Indian Council of Medical Research, National Institute for Research in Reproductive Health, Mumbai-400012, India.

ABSTRACT
Antimicrobial peptides (AMPs) are diverse, biologically active, essential components of the innate immune system. As compared to conventional antibiotics, AMPs exhibit broad spectrum antimicrobial activity, reduced toxicity and reduced microbial resistance. They are widely researched for their therapeutic potential, especially against multi-drug resistant pathogens. AMPs are known to have family-specific sequence composition, which can be mined for their discovery and rational design. Here, we present a detailed family-based study on AMP families. The study involved the use of sequence signatures represented by patterns and hidden Markov models (HMMs) present in experimentally studied AMPs to identify novel AMPs. Along with AMPs, peptides hitherto lacking antimicrobial annotation were also retrieved and wet-lab studies on randomly selected sequences proved their antimicrobial activity against Escherichia coli. CAMPSign, a webserver has been created for researchers to effortlessly exploit the use of AMP family signatures for identification of AMPs. The webserver is available online at www.campsign.bicnirrh.res.in. In this work, we demonstrate an optimised and experimentally validated protocol along with a freely available webserver that uses family-based sequence signatures for accelerated discovery of novel AMPs.

No MeSH data available.


Related in: MedlinePlus

Pattern-restricted multiple sequence alignment of the sequence retrieved using pattern of lactotransferrin with the experimentally validated sequences of lactotransferrin.
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f2: Pattern-restricted multiple sequence alignment of the sequence retrieved using pattern of lactotransferrin with the experimentally validated sequences of lactotransferrin.

Mentions: LactP represents the part of the retrieved sequence corresponding to the pattern identified for lactotransferrin. Since pattern captures the most conserved region of AMPs within a family, it is highly likely that the precise AMP region may not be captured in the pattern. In order to refine/determine the antimicrobial region, the retrieved sequence was aligned with the experimentally validated AMPs of the lactotransferrin family (Fig. 2). Based on the alignment and sequence conservation, two sequences with additional flanking residues (LactP1, LactP2) were synthesized (Table 2). Antimicrobial activity of these two peptides was studied against both the strains of E. coli (Table 3). LactP1 exhibited 50% inhibition at 100 microM against both the strains of E. coli whereas LactP2 which had more number of flanking residues exhibited 100% inhibition at 100 microM against one strain of E. coli. It is highly likely that if more flanking residues are considered and the region is further refined, the antimicrobial activity of the resulting peptides may be significantly enhanced.


Leveraging family-specific signatures for AMP discovery and high-throughput annotation.

Waghu FH, Barai RS, Idicula-Thomas S - Sci Rep (2016)

Pattern-restricted multiple sequence alignment of the sequence retrieved using pattern of lactotransferrin with the experimentally validated sequences of lactotransferrin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836297&req=5

f2: Pattern-restricted multiple sequence alignment of the sequence retrieved using pattern of lactotransferrin with the experimentally validated sequences of lactotransferrin.
Mentions: LactP represents the part of the retrieved sequence corresponding to the pattern identified for lactotransferrin. Since pattern captures the most conserved region of AMPs within a family, it is highly likely that the precise AMP region may not be captured in the pattern. In order to refine/determine the antimicrobial region, the retrieved sequence was aligned with the experimentally validated AMPs of the lactotransferrin family (Fig. 2). Based on the alignment and sequence conservation, two sequences with additional flanking residues (LactP1, LactP2) were synthesized (Table 2). Antimicrobial activity of these two peptides was studied against both the strains of E. coli (Table 3). LactP1 exhibited 50% inhibition at 100 microM against both the strains of E. coli whereas LactP2 which had more number of flanking residues exhibited 100% inhibition at 100 microM against one strain of E. coli. It is highly likely that if more flanking residues are considered and the region is further refined, the antimicrobial activity of the resulting peptides may be significantly enhanced.

Bottom Line: As compared to conventional antibiotics, AMPs exhibit broad spectrum antimicrobial activity, reduced toxicity and reduced microbial resistance.The webserver is available online at www.campsign.bicnirrh.res.in.In this work, we demonstrate an optimised and experimentally validated protocol along with a freely available webserver that uses family-based sequence signatures for accelerated discovery of novel AMPs.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Informatics Centre of Indian Council of Medical Research, National Institute for Research in Reproductive Health, Mumbai-400012, India.

ABSTRACT
Antimicrobial peptides (AMPs) are diverse, biologically active, essential components of the innate immune system. As compared to conventional antibiotics, AMPs exhibit broad spectrum antimicrobial activity, reduced toxicity and reduced microbial resistance. They are widely researched for their therapeutic potential, especially against multi-drug resistant pathogens. AMPs are known to have family-specific sequence composition, which can be mined for their discovery and rational design. Here, we present a detailed family-based study on AMP families. The study involved the use of sequence signatures represented by patterns and hidden Markov models (HMMs) present in experimentally studied AMPs to identify novel AMPs. Along with AMPs, peptides hitherto lacking antimicrobial annotation were also retrieved and wet-lab studies on randomly selected sequences proved their antimicrobial activity against Escherichia coli. CAMPSign, a webserver has been created for researchers to effortlessly exploit the use of AMP family signatures for identification of AMPs. The webserver is available online at www.campsign.bicnirrh.res.in. In this work, we demonstrate an optimised and experimentally validated protocol along with a freely available webserver that uses family-based sequence signatures for accelerated discovery of novel AMPs.

No MeSH data available.


Related in: MedlinePlus