**Table 1.** *ListofAMPwithactivityanti-*A.baumannii*.*

an *ex vivo* human skin infection model and an *in vivo* murine skin infection model at concentrations above 5% [74].

#### *2.1.2 Snake cathelicidins*

The anti-*A. baumannii* activity among the cathelicidins isolated from snakes has been reported for the peptides cathelicidin-BF (Cath-BF) [75] and *Naja atra* cathelicidin (NA-CATH). One of the best-known cathelicidins is Cath-BF having an α-helical structure, isolated from the venous glands of the species *Bungatus fasciatus* [152]. It has been shown that Cath-BF causes bacterial death through two bacterial membrane disruption mechanisms and attacking intracellular targets [152]. According to available reports, this peptide is highly active against drug-resistant clinical isolates of *A. baumannii*, inhibiting its growth around 12.8 μg/ml concentration [75]. ZY4 cathelicidin-BF-15 derived, a cyclic peptide stabilized by a disulfide bridge with high stability *in vivo* (the half-life is 1.8 h), showed excellent activity against *A. baumannii*, including standard clinical MDR strains with MIC values ranging between 4.6 and 9.4 μg/mL. ZY4 killed bacteria by permeabilizing the bacterial membrane showed a low propensity to induce resistance, exhibited biofilm inhibition and eradication activities, and killed persister cells [76]. The peptide NA-CATH, produced by a cobra called *N. atra*, possesses an α-helical structure at N-terminal and an unstructured segment at C-terminal [77, 153]. This peptide exerts antimicrobial activity through the membrane lysis by membrane thinning or transient pore formation [154] and is highly active against drugresistant and sensitive *A. baumannii* strains, completely inhibiting bacterial growth at a concentration of 10 μg/ml [77, 153]. In 2018, Zhao et al. identified a novel cathelicidin (OH-CATH) from the king cobra, with its analog DOH-CATH30 found to exhibit potent microbicidal activity (MIC 1.56 to 12.5 μg/mL) against several Gram-negative and Gram-positive bacteria, including MDR *A. baumannii* [78]. Other cathelicidins with antimicrobial activity, identified in the venous glands, are OH-CATH30, from the venom of the cobra and mirtoxin, from *Myrmecia pilosula* [78, 79], presenting antimicrobial activity through inhibition of planktonic bacterial growth and biofilm, eradication of persistent bacterial cells, and inhibition of inflammatory process [76, 78].

Compounds with similar activity have been identified in the venom of some scorpion species and tested against antibiotic-resistant bacteria. Therefore, Al-Asmari et al. evaluate the *in vitro* antimicrobial activities of the toxins extracted from three medically necessary Saudi Scorpions. Among these, only *Leiurus quinquestriatus* showed significant broad-spectrum antimicrobial activity in a dosedependent manner from 5 to 20 mg/mL, inhibiting 50.6% of growth and survival of MDR *A. baumannii* [80]. High antimicrobial activity was also observed for AMPs ranalexin and danalexin obtained from *Rana catesbeiana* [81], LS-sarcotoxin, and LS-stomoxyn (*Lucilla serricata*) [82], and minibactenecins *(Capra hircus*) [83]. However, further *in vivo* studies are needed to improve the pharmacokinetics of systemic administration and find solutions to avoid their degradation by proteases despite the antimicrobial activity on *A. baumannii* strains of these compounds.

#### *2.1.3 Alligator cathelicidins*

Alligator mississippiensis (American alligator), a member of order Crocodilia, lives in bacteria-laden environments but cannot often succumb to bacterial infections. Serum of alligators has antibacterial activity beyond that of human sérum [155], killing a wide range of pathogens, and it is believed that this activity is attributable at least partially to the presence of CAMPs in the alligator plasma and

extracts [156]. A study by Barksdale et al. (2017) reported the anti-*A. baumannii* effect of AMPs produced by American alligator: cathelicidin called AM-CATH36 and its two fragments including AM-CATH28 and AM-CATH21 [77]. Alligator cathelicidin can inhibit the growth of both drug-resistant and sensitive *A. baumannii* at the 2.5 μg/ml concentration. Furthermore, two shorter fragments of this peptide can inhibit the drug-resistant *A. baumannii* at a 10 μg/ml concentration. The anti-*A. baumannii* effect of these three peptides is through membrane permeabilization. Interestingly, MDR clinical isolates of *A. baumannii* were more susceptible to both the AM CATH21 and AM-CATH28 peptides than the sensitive strains.
