In vitro activity of protegrin-1 and beta-defensin-1, alone and in combination with isoniazid, against Mycobacterium tuberculosis

Fattorini, Lanfranco; Gennaro, Renato; Zanetti, Margherita; Tan, Dejiang; Brunori, Lara; Giannoni, Federico; Pardini, Manuela; Orefici, Graziella

doi:10.1016/j.peptides.2004.04.003

Cited by 61 publications

(49 citation statements)

References 13 publications

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“…Minimal inhibitory concentrations (MICs) for defensins and LL-37 against these pathogens can range from less than 10 μg/mL to greater than 250 μg/mL (Miyakawa et al , 1996; Saiman et al , 2001; Starner et al , 2005) (Table 1). However, the susceptibility of a given species is often strain-specific and dependent on conditions, including salt concentration and interaction with other antimicrobials (Bals et al , 1998a; Garcia et al , 2001b; Starner et al , 2002; Fattorini et al , 2004). …”

Section: Defense Against Microbial Infectionsmentioning

confidence: 99%

Host Defense Peptides in the Oral Cavity and the Lung: Similarities and Differences

Diamond

Beckloff²,

Ryan³

2008

J Dent Res

153

150

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Peptides with broad-spectrum antimicrobial activity are found in the mucosal surfaces at many sites in the body, including the airway, the oral cavity, and the digestive tract. Based on their in vitro antimicrobial and other immunomodulatory activities, these host defense peptides have been proposed to play an important role in the innate defense against pathogenic microbial colonization. The genes that encode these peptides are up-regulated by pathogens, further supporting their role in innate immune defense. However, the differences in the local microbial environments between the generally sterile airway and the highly colonized oral cavity suggest a more complex role for these peptides in innate immunity. For example, β-defensin genes are induced in the airway by all bacteria and Toll-like receptor (TLR) agonists primarily through an NF-κB-mediated pathway. In contrast, the same genes are induced in the gingival epithelium by only a subset of bacteria and TLR ligands, via different pathways. Furthermore, the environments into which the peptides are secretedspecifically saliva, gingival crevicular fluid, and airway surface fluid-differ greatly and can effect their respective activities in host defense. In this review, we examine the differences and similarities between host defense peptides in the oral cavity and the airway, to gain a better understanding of their contributions to immunity.

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Section: Defense Against Microbial Infectionsmentioning

confidence: 99%

Host Defense Peptides in the Oral Cavity and the Lung: Similarities and Differences

Diamond

Beckloff²,

Ryan³

2008

J Dent Res

153

150

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“…To minimize the development of antibiotic resistance and to retain consumer confidence in food safety, alternative approaches of controlling infection in animal production are needed. Protegrin-1 (PG-1), one of the most potent antimicrobial peptides (1,11,39), targets both gram-negative and grampositive bacteria, including bacteria that demonstrate in vivo antibiotic resistance (11,21,27,32,34). In addition, it has been shown to reduce lentiviral infectivity and to have activity against enveloped viruses, including human immunodeficiency virus (33,34).…”

mentioning

confidence: 99%

Enhanced Resistance to Bacterial Infection in Protegrin-1 Transgenic Mice

Cheung¹,

Turner²,

Song³

et al. 2008

Antimicrob Agents Chemother

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Antibiotic-resistant bacteria have become a public health concern. It was suggested that one source of resistant pathogens may be food-producing animals. Alternative approaches are therefore needed to enhance the resistance of farm animals to bacterial infection. Protegrin-1 (PG-1) is a neutrophil-derived antimicrobial peptide that possesses activity against a wide range of bacteria and enveloped viruses. Here we report on the production of transgenic mice that ectopically expressed PG-1 and compare their susceptibilities to Actinobacillus suis infection with those of their wild-type (WT) littermates. Of the 126 mice that were challenged with A. suis, 87% of the transgenic mice survived, whereas 31% of their WT littermates survived. The PG-1 transgenic mice had significantly lower bacterial loads in their lungs and reduced numbers of pulmonary pathological lesions. The antimicrobial function of PG-1 was confirmed in vitro by using fibroblast cells isolated from the transgenic mice but not the WT mice. Moreover, differential blood cell counts in bronchoalveolar lavage fluid indicated greater number of neutrophils in PG-1 transgenic mice than in their WT littermates after bacterial challenge. Our data suggest that the ectopic expression of PG-1 in mice confers enhanced resistance to bacterial infection, laying the foundation for the development of livestock with improved resistance to infection.

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“…As a first line of innate host defense against invading pathogens, AMPs can exert significant immune modulatory activity on mammalian cells [58]. In this respect, human alpha-helical LL-37 cathelicidin has been extensively studied [17,21,57,59,60].…”

Section: Resultsmentioning

confidence: 99%

“…The stock solutions were prepared in 0.1% aqueous acetic acid and were ultrafiltered prior to their use. When tested for their antimicrobial activity against Neisseria gonorrhoeae strain FA19 [58], PG-1 ( 1 ) and its linearized analog ( 8 ) demonstrated similar potencies to those published under similar conditions [87]. …”

Section: Methodsmentioning

confidence: 99%

Structure-Dependent Immune Modulatory Activity of Protegrin-1 Analogs

2014

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Protegrins are porcine antimicrobial peptides (AMPs) that belong to the cathelicidin family of host defense peptides. Protegrin-1 (PG-1), the most investigated member of the protegrin family, is an arginine-rich peptide consisting of 18 amino acid residues, its main chain adopting a β-hairpin structure that is linked by two disulfide bridges. We report on the immune modulatory activity of PG-1 and its analogs in neutralizing bacterial endotoxin and capsular polysaccharides, consequently inhibiting inflammatory mediators’ release from macrophages. We demonstrate that the β-hairpin structure motif stabilized with at least one disulfide bridge is a prerequisite for the immune modulatory activity of this type of AMP.

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In vitro activity of protegrin-1 and beta-defensin-1, alone and in combination with isoniazid, against Mycobacterium tuberculosis

Cited by 61 publications

References 13 publications

Host Defense Peptides in the Oral Cavity and the Lung: Similarities and Differences

Host Defense Peptides in the Oral Cavity and the Lung: Similarities and Differences

Enhanced Resistance to Bacterial Infection in Protegrin-1 Transgenic Mice

Structure-Dependent Immune Modulatory Activity of Protegrin-1 Analogs

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