Cathelicidins are a major family of antimicrobial peptides present in vertebrate animals with potent microbicidal and immunomodulatory activities. Four cathelicidins, namely fowlicidins 1 to 3 and cathelicidin B1, hav...Cathelicidins are a major family of antimicrobial peptides present in vertebrate animals with potent microbicidal and immunomodulatory activities. Four cathelicidins, namely fowlicidins 1 to 3 and cathelicidin B1, have been identified in chickens. As a first step to understand their role in early innate host defense of chickens, we examined the tissue and developmental expression patterns of all four cathelicidins. Real-time PCR revealed an abundant expression of four cathelicidins throughout the gastrointestinal, respiratory, and urogenital tracts as well as in all primary and secondary immune organs of chickens. Fowlicidins 1 to 3 exhibited a similar tissue expression pattern with the highest expression in the bone marrow and lung, while cathelicidin B1 was synthesized most abundantly in the bursa of Fabricius. Additionally, a tissue-specific regulatory pattern was evident for all four cathelicidins during the first 28 days after hatching. The expression of fowlicidins 1 to 3 showed an age-dependent increase both in the cecal tonsil and lung, whereas all four cathelicidins were peaked in the bursa on day 4 after hatching, with a gradual decline by day 28. An abrupt augmentation in the expression of fowlicidins 1 to 3 was also observed in the cecum on day 28, while the highest expression of cathelicidin B1 was seen in both the lung and cecal tonsil on day 14. Collectively, the presence of cathelicidins in a broad range of tissues and their largely enhanced expression during development are suggestive of their potential important role in early host defense and disease resistance of chickens.展开更多
Cathelicidin Pc-CATH1 is a cathelicidin-derived myeloid antimicrobial peptide identified from Phasianus colchicus with strong antimicrobial activity against most of bacteria and fungi tested,including the clinically i...Cathelicidin Pc-CATH1 is a cathelicidin-derived myeloid antimicrobial peptide identified from Phasianus colchicus with strong antimicrobial activity against most of bacteria and fungi tested,including the clinically isolated(IS)drug-resistant strains.Considering the uniform distribution of net positive charge in both C-and N-terminus sequence of cathelicidin Pc-CATH1 and most of hydrophobic amino acid(aa)residues positioned in middle of the sequence,the antimicrobial peptide was used to investigate the structure-function relationship by truncating gradually N-or C-terminus amino acid residue.More than 10 modified peptide homo-logues(20-26 aa length)of cathelicidin Pc-CATH1 were found to keep strong antimicrobial abilities.The possible relationships between bioactivities including antimicrobial and hemolytic abilities,components of secondary structure,hydrophobicity,amphipathicity,net charge,and sequence length were investigated.The current work provided suggestions for structural and functional modification of linear,α-helical antimicrobial peptides containing no disulfided bridges.展开更多
Natural antimicrobial peptides (AMPs) are small cationic molecules that display antimicrobial activity against a wide range of bacteria, fungi and viruses. AMPs are multifunctional molecules that have an essential act...Natural antimicrobial peptides (AMPs) are small cationic molecules that display antimicrobial activity against a wide range of bacteria, fungi and viruses. AMPs are multifunctional molecules that have an essential activity in infection and inflammation: they play an important role in the innate immune response, not only as antimicrobial agents, but also as immunomodulating molecules and as an important link between the innate and adaptive immune response. In this article, we will discuss the antimicrobial activity, together with the novel properties of some of these molecules as immune modulators on the innate and adaptive immune response.展开更多
Microbial resistance has now become a global public health concern,and the spread of multidrug-resistant bacteria also threatens human health.Antimicrobial peptides(AMPs)are a class of small peptides with antibacteria...Microbial resistance has now become a global public health concern,and the spread of multidrug-resistant bacteria also threatens human health.Antimicrobial peptides(AMPs)are a class of small peptides with antibacterial,anti-inflammatory,anti-infective,antioxidation,anti-tumor,antiviral functions and immune regulation activities.Due to the small sizes,their structures are easily studied by nuclear magnetic resonance(NMR)techniques.Compared to traditional antibiotics,AMPs have specific antibacterial mechanisms,and do not easily result in the production of drug-resistant strains.Thus,the development of new antimicrobial peptides and their wide use instead of chemical antibiotics are of great significance to human health.In this review,we first summarized the relationship between the structures and functions of antimicrobial peptides.Then,we focused on examples,cathelicidins,a group of cationic antimicrobial peptides with multiple biological activities.Especially,cathelicidin BF30 or BF34,composed of 30 or 34 amino acids,were from the venom glands of the Bungarus fasciatus snake and were considered to be the most active antibacterial peptides among different cathelicidin members.Their solution structures determined by NMR are a-helixes,which are useful in designing new and stable peptides with similar framework,including stapple peptides by inducing chemical modifications in the sidechains of some residues,as well as cyclic peptides by inducing disulfide bond between cysteines in the sequences.展开更多
Antimicrobial peptides（AMPs）,a class of gene-encoded peptides,are the first line of immune system to defense microbial invasions in multicellular organisms.Cathelicidins are an important family of AMPs that have bee...Antimicrobial peptides（AMPs）,a class of gene-encoded peptides,are the first line of immune system to defense microbial invasions in multicellular organisms.Cathelicidins are an important family of AMPs that have been identified exclusively in vertebrates.However,up to now,cathelicidins from amphibians are poorly understood.In the present study,we reported the identification and characterization of two novel cathelicidins（FM-CATH1 and FMCATH2） from the frog Fejervarya multistriata.The c DNA sequences encoding FM-CATHs were successfully cloned from the constructed lung c DNA library of F.multistriata.Both of the c DNA sequences encoding FM-CATHs are 447 bp in length,and the deduced mature peptides of FM-CATHs are composed of 34 residues.Structural analysis indicated that FM-CATH1 and FM-CATH2 mainly assume amphipathic alpha-helical conformations.Antimicrobial and bacterial killing kinetic analysis indicated that both FM-CATH1 and FM-CATH2 possess potent,broad-spectrum and rapid antimicrobial potency.And cytoplasmic membrane permeabilization analysis indicated that FM-CATH1 and FMCATH2 kill bacteria by inducing the permeabilization of bacterial membrane.Besides direct antimicrobial activities,FM-CATHs also exhibited significant inhibitory effect on the formation of bacterial biofilms at low concentrations below 1×MIC.Furthermore,FM-CATH1 and FM-CATH2 exhibited potent anti-inflammatory activities by inhibiting LPS-induced transcription and production of pro-inflammatory cytokines TNF-α,IL-1β,and IL-6 in mouse peritoneal macrophages.Meanwhile,FM-CATHs showed relatively low cytotoxic activity against mammalian normal and tumor cell lines,and low hemolytic activity against human erythrocytes.In summary,the identification of FM-CATHs provides novel clues for our understanding of the roles of cathelicidins in amphibian immune systems.The potent antimicrobial,biofilm inhibitory,anti-inflammatory activities,and low cytotoxicity of FM-CATHs imply their great potential in novel antibiotics development.展开更多
Antimicrobial peptides(AMPs) are a group of gene-encoded small peptides that play pivotal roles in the host immune system of multicellular organisms.Cathelicidins are an important family of AMPs that exclusively exist...Antimicrobial peptides(AMPs) are a group of gene-encoded small peptides that play pivotal roles in the host immune system of multicellular organisms.Cathelicidins are an important family of AMPs that exclusively exist in vertebrates. Many cathelicidins have been identified from mammals, birds, reptiles and fish. To date, however, cathelicidins from amphibians are poorly understood. In the present study, two novel cathelicidins(OL-CATH1 and 2) were identified and studied from the odorous frog Odorrana livida.Firstly, the cDNAs encoding the OL-CATHs(780 and735 bp in length, respectively) were successfully cloned from a lung cDNA library constructed for the frog. Multi-sequence alignment was carried out to analyze differences between the precursors of the OL-CATHs and other representative cathelicidins.Mature peptide sequences of OL-CATH1 and 2 were predicted(33 amino acid residues) and their secondary structures were determined(OL-CATH1 showed a random-coil conformation and OL-CATH2 demonstrated α-helical conformation). Furthermore,OL-CATH1 and 2 were chemically synthesized and their in vitro functions were determined. Antimicrobial and bacterial killing kinetic analyses indicated that OL-CATH2 demonstrated relatively moderate and rapid antimicrobial potency and exhibited strong anti-inflammatory activity. At very low concentrations(10 μg/mL), OL-CATH2 significantly inhibited the lipopolysaccharide(LPS)-induced transcription and production of pro-inflammatory cytokines TNF-α, IL-1βand IL-6 in mouse peritoneal macrophages. In contrast, OL-CATH1 did not exhibit any detectableantimicrobial or anti-inflammatory activities. Overall,identification of these OL-CATHs from O. livida enriches our understanding of the functions of cathelicidins in the amphibian immune system. The potent antimicrobial and anti-inflammatory activities of OL-CATH2 highlight its potential as a novel candidate in anti-infective drug development.展开更多
BACKGROUND： Periodomitis i.e. inflammation of the periodontium is a multifactorial disease. Antimicrobial peptides （AMPs） which demonstrate a broad-spectrum of activity against varied number of bacteria, fungi, vir...BACKGROUND： Periodomitis i.e. inflammation of the periodontium is a multifactorial disease. Antimicrobial peptides （AMPs） which demonstrate a broad-spectrum of activity against varied number of bacteria, fungi, viruses, and parasites, and cancerous cells have been linked to periodontitis. The AMPs even possess the caliber of immunomodulation, and are significantly responsive to innate immuno-stimulation and infections. LL-37 plays a salubrious role by preventing and in treatment of chronic forms of periodontitis. OBJECTIVE： In the present work we will review the role of antimicrobial peptide LL-37 in periodontitis. METHODS： A systematic search was carried out from the beginning till August, 2016 using the Pubmed search engine. The keywords included ＂LL-37,＂ ＂periodontitis,＂ ＂Papillon-Lefevre syndrome,＂ ＂Morbus Kostmann,＂ ＂Haim-Munk syndrome＂ along with use of Boolean operator ＂and.＂ RESULTS： The search resulted in identifying 67 articles which included articles linking LL-37 with periodontitis, articles on Papillon-Lefevre syndrome, Morbus Kostmann, Haim-Munk syndrome, LL-37 and periodontitis and articles on pathogenicity of periodontitis. CONCLUSION： The literature search concluded that LL-37 plays a pivotal role in preventing and treatment of severe form of periodontitis.展开更多
基金supported by a United States Department of Agriculture grant2008-35204-04544Oklahoma Center for the Advancement of Science and Technology grants HR07-113, and AR07.2-087, and Oklahoma Agricultural Experiment Station project H-2811
文摘Cathelicidins are a major family of antimicrobial peptides present in vertebrate animals with potent microbicidal and immunomodulatory activities. Four cathelicidins, namely fowlicidins 1 to 3 and cathelicidin B1, have been identified in chickens. As a first step to understand their role in early innate host defense of chickens, we examined the tissue and developmental expression patterns of all four cathelicidins. Real-time PCR revealed an abundant expression of four cathelicidins throughout the gastrointestinal, respiratory, and urogenital tracts as well as in all primary and secondary immune organs of chickens. Fowlicidins 1 to 3 exhibited a similar tissue expression pattern with the highest expression in the bone marrow and lung, while cathelicidin B1 was synthesized most abundantly in the bursa of Fabricius. Additionally, a tissue-specific regulatory pattern was evident for all four cathelicidins during the first 28 days after hatching. The expression of fowlicidins 1 to 3 showed an age-dependent increase both in the cecal tonsil and lung, whereas all four cathelicidins were peaked in the bursa on day 4 after hatching, with a gradual decline by day 28. An abrupt augmentation in the expression of fowlicidins 1 to 3 was also observed in the cecum on day 28, while the highest expression of cathelicidin B1 was seen in both the lung and cecal tonsil on day 14. Collectively, the presence of cathelicidins in a broad range of tissues and their largely enhanced expression during development are suggestive of their potential important role in early host defense and disease resistance of chickens.
基金supported by Chinese National Natural Science Foundation(31070701,31000962,31025025,30730026)the Program of Shanghai Subject Chief Scientist(NO.09XD1405100)+1 种基金the Ministry of Science and Technology(2010CB529800,2009ZX09103-1/091,2011ZX09102-002-10)the Ministry of Agriculture(2009ZX08009-159B).
文摘Cathelicidin Pc-CATH1 is a cathelicidin-derived myeloid antimicrobial peptide identified from Phasianus colchicus with strong antimicrobial activity against most of bacteria and fungi tested,including the clinically isolated(IS)drug-resistant strains.Considering the uniform distribution of net positive charge in both C-and N-terminus sequence of cathelicidin Pc-CATH1 and most of hydrophobic amino acid(aa)residues positioned in middle of the sequence,the antimicrobial peptide was used to investigate the structure-function relationship by truncating gradually N-or C-terminus amino acid residue.More than 10 modified peptide homo-logues(20-26 aa length)of cathelicidin Pc-CATH1 were found to keep strong antimicrobial abilities.The possible relationships between bioactivities including antimicrobial and hemolytic abilities,components of secondary structure,hydrophobicity,amphipathicity,net charge,and sequence length were investigated.The current work provided suggestions for structural and functional modification of linear,α-helical antimicrobial peptides containing no disulfided bridges.
文摘Natural antimicrobial peptides (AMPs) are small cationic molecules that display antimicrobial activity against a wide range of bacteria, fungi and viruses. AMPs are multifunctional molecules that have an essential activity in infection and inflammation: they play an important role in the innate immune response, not only as antimicrobial agents, but also as immunomodulating molecules and as an important link between the innate and adaptive immune response. In this article, we will discuss the antimicrobial activity, together with the novel properties of some of these molecules as immune modulators on the innate and adaptive immune response.
基金National Science Foundation of China(NSFC)under No.22174155,22177127 and 21977110.
文摘Microbial resistance has now become a global public health concern,and the spread of multidrug-resistant bacteria also threatens human health.Antimicrobial peptides(AMPs)are a class of small peptides with antibacterial,anti-inflammatory,anti-infective,antioxidation,anti-tumor,antiviral functions and immune regulation activities.Due to the small sizes,their structures are easily studied by nuclear magnetic resonance(NMR)techniques.Compared to traditional antibiotics,AMPs have specific antibacterial mechanisms,and do not easily result in the production of drug-resistant strains.Thus,the development of new antimicrobial peptides and their wide use instead of chemical antibiotics are of great significance to human health.In this review,we first summarized the relationship between the structures and functions of antimicrobial peptides.Then,we focused on examples,cathelicidins,a group of cationic antimicrobial peptides with multiple biological activities.Especially,cathelicidin BF30 or BF34,composed of 30 or 34 amino acids,were from the venom glands of the Bungarus fasciatus snake and were considered to be the most active antibacterial peptides among different cathelicidin members.Their solution structures determined by NMR are a-helixes,which are useful in designing new and stable peptides with similar framework,including stapple peptides by inducing chemical modifications in the sidechains of some residues,as well as cyclic peptides by inducing disulfide bond between cysteines in the sequences.
基金supported by the grants BK20160336 from the Natural Science Foundation of Jiangsu Province to Yan CHEN16KJB350004 from the Natural Science Foundation of College in Jiangsu Province to Yipeng WANG+1 种基金SYN201407 and SYN201504 from the Suzhou Science and Technology Development Project to Yipeng WANG2015NY06 from the Haimen Science and Technology Development Project to Yipeng WANG
文摘Antimicrobial peptides（AMPs）,a class of gene-encoded peptides,are the first line of immune system to defense microbial invasions in multicellular organisms.Cathelicidins are an important family of AMPs that have been identified exclusively in vertebrates.However,up to now,cathelicidins from amphibians are poorly understood.In the present study,we reported the identification and characterization of two novel cathelicidins（FM-CATH1 and FMCATH2） from the frog Fejervarya multistriata.The c DNA sequences encoding FM-CATHs were successfully cloned from the constructed lung c DNA library of F.multistriata.Both of the c DNA sequences encoding FM-CATHs are 447 bp in length,and the deduced mature peptides of FM-CATHs are composed of 34 residues.Structural analysis indicated that FM-CATH1 and FM-CATH2 mainly assume amphipathic alpha-helical conformations.Antimicrobial and bacterial killing kinetic analysis indicated that both FM-CATH1 and FM-CATH2 possess potent,broad-spectrum and rapid antimicrobial potency.And cytoplasmic membrane permeabilization analysis indicated that FM-CATH1 and FMCATH2 kill bacteria by inducing the permeabilization of bacterial membrane.Besides direct antimicrobial activities,FM-CATHs also exhibited significant inhibitory effect on the formation of bacterial biofilms at low concentrations below 1×MIC.Furthermore,FM-CATH1 and FM-CATH2 exhibited potent anti-inflammatory activities by inhibiting LPS-induced transcription and production of pro-inflammatory cytokines TNF-α,IL-1β,and IL-6 in mouse peritoneal macrophages.Meanwhile,FM-CATHs showed relatively low cytotoxic activity against mammalian normal and tumor cell lines,and low hemolytic activity against human erythrocytes.In summary,the identification of FM-CATHs provides novel clues for our understanding of the roles of cathelicidins in amphibian immune systems.The potent antimicrobial,biofilm inhibitory,anti-inflammatory activities,and low cytotoxicity of FM-CATHs imply their great potential in novel antibiotics development.
基金supported by grants from the Jiangsu Students' Innovation and Entrepreneurship Training Program(2017suda098)the National Natural Science Foundation of China(31772455)+2 种基金Natural Science Foundation of Jiangsu Province(BK20160336 and BK20171214)Natural Science Foundation of College in Jiangsu Province(16KJB350004)Suzhou Science and Technology Development Project(SYN201504 and SNG2017045)
文摘Antimicrobial peptides(AMPs) are a group of gene-encoded small peptides that play pivotal roles in the host immune system of multicellular organisms.Cathelicidins are an important family of AMPs that exclusively exist in vertebrates. Many cathelicidins have been identified from mammals, birds, reptiles and fish. To date, however, cathelicidins from amphibians are poorly understood. In the present study, two novel cathelicidins(OL-CATH1 and 2) were identified and studied from the odorous frog Odorrana livida.Firstly, the cDNAs encoding the OL-CATHs(780 and735 bp in length, respectively) were successfully cloned from a lung cDNA library constructed for the frog. Multi-sequence alignment was carried out to analyze differences between the precursors of the OL-CATHs and other representative cathelicidins.Mature peptide sequences of OL-CATH1 and 2 were predicted(33 amino acid residues) and their secondary structures were determined(OL-CATH1 showed a random-coil conformation and OL-CATH2 demonstrated α-helical conformation). Furthermore,OL-CATH1 and 2 were chemically synthesized and their in vitro functions were determined. Antimicrobial and bacterial killing kinetic analyses indicated that OL-CATH2 demonstrated relatively moderate and rapid antimicrobial potency and exhibited strong anti-inflammatory activity. At very low concentrations(10 μg/mL), OL-CATH2 significantly inhibited the lipopolysaccharide(LPS)-induced transcription and production of pro-inflammatory cytokines TNF-α, IL-1βand IL-6 in mouse peritoneal macrophages. In contrast, OL-CATH1 did not exhibit any detectableantimicrobial or anti-inflammatory activities. Overall,identification of these OL-CATHs from O. livida enriches our understanding of the functions of cathelicidins in the amphibian immune system. The potent antimicrobial and anti-inflammatory activities of OL-CATH2 highlight its potential as a novel candidate in anti-infective drug development.
文摘BACKGROUND： Periodomitis i.e. inflammation of the periodontium is a multifactorial disease. Antimicrobial peptides （AMPs） which demonstrate a broad-spectrum of activity against varied number of bacteria, fungi, viruses, and parasites, and cancerous cells have been linked to periodontitis. The AMPs even possess the caliber of immunomodulation, and are significantly responsive to innate immuno-stimulation and infections. LL-37 plays a salubrious role by preventing and in treatment of chronic forms of periodontitis. OBJECTIVE： In the present work we will review the role of antimicrobial peptide LL-37 in periodontitis. METHODS： A systematic search was carried out from the beginning till August, 2016 using the Pubmed search engine. The keywords included ＂LL-37,＂ ＂periodontitis,＂ ＂Papillon-Lefevre syndrome,＂ ＂Morbus Kostmann,＂ ＂Haim-Munk syndrome＂ along with use of Boolean operator ＂and.＂ RESULTS： The search resulted in identifying 67 articles which included articles linking LL-37 with periodontitis, articles on Papillon-Lefevre syndrome, Morbus Kostmann, Haim-Munk syndrome, LL-37 and periodontitis and articles on pathogenicity of periodontitis. CONCLUSION： The literature search concluded that LL-37 plays a pivotal role in preventing and treatment of severe form of periodontitis.
