Reptilian β-defensins: Expanding the repertoire of known crocodylian peptides

Santana, Felix L.; Estrada, Karel; Ortíz, Ernesto; Corzo, Gerardo

doi:10.1016/j.peptides.2020.170473

Cited by 8 publications

(8 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bioinformatic strategies have enabled new possibilities for the identification of HDPs in lesser-studied species, such as crocodylians [ 42 ]. Previously, HMMs have been successfully used to explore cathelicidin peptides in several vertebrate species [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens

et al. 2022

Self Cite

View full text Add to dashboard Cite

Host defense peptides (HDPs) represent an alternative way to address the emergence of antibiotic resistance. Crocodylians are interesting species for the study of these molecules because of their potent immune system, which confers high resistance to infection. Profile hidden Markov models were used to screen the genomes of four crocodylian species for encoded cathelicidins and eighteen novel sequences were identified. Synthetic cathelicidins showed broad spectrum antimicrobial and antibiofilm activity against several clinically important antibiotic-resistant bacteria. In particular, the As-CATH8 cathelicidin showed potent in vitro activity profiles similar to the last-resort antibiotics vancomycin and polymyxin B. In addition, As-CATH8 demonstrated rapid killing of planktonic and biofilm cells, which correlated with its ability to cause cytoplasmic membrane depolarization and permeabilization as well as binding to DNA. As-CATH8 displayed greater antibiofilm activity than the human cathelicidin LL-37 against methicillin-resistant Staphylococcus aureus in a human organoid model of biofilm skin infection. Furthermore, As-CATH8 demonstrated strong antibacterial effects in a murine abscess model of high-density bacterial infections against clinical isolates of S. aureus and Acinetobacter baumannii, two of the most common bacterial species causing skin infections globally. Overall, this work expands the repertoire of cathelicidin peptides known in crocodylians, including one with considerable therapeutic promise for treating common skin infections.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…The rapid divergence of mammalian β-defensins following gene duplication events was previously found to be driven by positive selection [4,5]. Positive selection is thought to have also occurred in reptilian and avian β-defensins [6,20]. A previous study on avian β-defensins demonstrated that the effect of such selection, however, was very weak in AvBD9, AvBD11, and AvBD13 [6].…”

Section: Analysis Of Positive Selection and Detection Of Amino Acids ...mentioning

confidence: 96%

“…OvoD sequences from these species were obtained from two previous studies [7,8]. Beta-defensin sequences from four crocodile species (Alligator mississippiensis, American alligator; Alligator sinensis, Chinese alligator; Crocodylus porosus, saltwater crocodile; Gavialis gangeticus, gharial) were taken from a recent work [20]. Putative β-defensin sequences from turtle species (Chrysemys picta bellii, western painted turtle; Chelydra serpentina, common snapping turtle; Pelusios castaneus, West African mud turtle; Terrapene Carolina triunguis, three-toed box turtle) were retrieved from annotated genes in the Ensembl database.…”

Section: Protein Sequences and Net Charge Determinationmentioning

confidence: 99%

“…Crocodiles are the closest relatives of birds in the Sauropsida clade (Figure 2). Santana and colleagues recently characterized a cluster of putative β-defensin-coding genes in the genomes of four crocodilian species, namely the saltwater crocodile (Crocodylus porosus), the American alligator (Alligator mississipiensis), the Chinese alligator (Alligator sinensis), and the gharial (Gavialis gangeticus) [20]. Therefore, we explored eventual phylogenetic relationships of β-defensins between birds and crocodiles.…”

Section: Phylogeny Of N-and C-terminal Domains Of Avbd11 Among Avbds ...mentioning

confidence: 99%

“…The presence of defensins or defensin-like peptides with multiple β-defensin motifs (two or more) is rare in vertebrates. Intriguingly, some have been found in lizards (green anole [17], Gila monsters [18], Komodo dragon [19]), but not in other reptiles, such as crocodiles [20] or turtles [21]. To our knowledge, they have never been reported in mammals, and our search for such "polydefensins" in mammals has been unsuccessful.…”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

The Two Domains of the Avian Double-β-Defensin AvBD11 Have Different Ancestors, Common with Potential Monodomain Crocodile and Turtle Defensins

Guyot

Landon

Monget

2022

Biology

View full text Add to dashboard Cite

Beta-defensins are an essential group of cysteine-rich host-defence peptides involved in vertebrate innate immunity and are generally monodomain. Among bird defensins, the avian β-defensin 11 (AvBD11) is unique because of its peculiar structure composed of two β-defensin domains. The reasons for the appearance of such ‘polydefensins’ during the evolution of several, but not all branches of vertebrates, still remain an open question. In this study, we aimed at exploring the origin and evolution of the bird AvBD11 using a phylogenetic approach. Although they are homologous, the N- and C-terminal domains of AvBD11 share low protein sequence similarity and possess different cysteine spacing patterns. Interestingly, strong variations in charge properties can be observed on the C-terminal domain depending on bird species but, despite this feature, no positive selection was detected on the AvBD11 gene (neither on site nor on branches). The comparison of AvBD11 protein sequences in different bird species, however, suggests that some amino acid residues may have undergone convergent evolution. The phylogenetic tree of avian defensins revealed that each domain of AvBD11 is distant from ovodefensins (OvoDs) and may have arisen from different ancestral defensins. Strikingly, our phylogenetic analysis demonstrated that each domain of AvBD11 has common ancestors with different putative monodomain β-defensins from crocodiles and turtles and are even more closely related with these reptilian defensins than with their avian paralogs. Our findings support that AvBD11′s domains, which differ in their cysteine spacing and charge distribution, do not result from a recent internal duplication but most likely originate from a fusion of two different ancestral genes or from an ancestral double-defensin arisen before the Testudines-Archosauria split.

show abstract