## 2 Results and Discussion
### Microbial Focus
Dental caries is an oral disease associated with microbial biofilm. The pH in these biofilms is low (pH5.5) due to the metabolic activity of the cariogenic bacteria. [PERSON] et al. conjugated the phototherapeutic agent protoporphyrin IX to the synthetic AMP P12 to enable antimicrobial activity at acidic pH [75]. Honey-derived exosome-like extracellular vesicles (HEc-EVs) were shown to contain a number of AMPs (defensin-1, jelleine 3, and MRJP1) as cargo molecules and bear antibiofilm capacity. Antiboofilm activity was stronger to _S. mutans_ than _S.anguinis_ and related to the induction of membrane damage [76]. [PERSON] et al. incorporated the AMP nisin into a single bond universal adhesive (at 3% \(w/v\)), which could inhibit the growth of _S. mutans_ monospecific biofilms, as well as that of saliva-derived multispecies biofilms. Reduced biofilm growth resulted from an inhibitory effect on EPS synthesis and/or excretion [77]. _S. mutans_ growth was also inhibited by the strong membrane disrupting activity of the lactotransferrin-derived AMP LF1 [78]. [PERSON] et al. reported on the effect of lysozyme, lactoferrin, and LL-37 on _S. pneumoniae_ serotype 23F, which is associated with respiratory infections. Although a combination of all three AMPs inhibited biofilm-derived bacterial activity, they did not affect the growth of persister cells [79]. _Fungi_  
The majority of publications on AMP as treatment for fungi focused on _C. albicans_, which can cause relatively simple to life-threatening invasive infections. The formation of biofilms on tissues and medical devices makes these infections more difficult to treat as they have become less susceptible to antifungal agents. Derivatives (specifically AMP3) of the innate immunity defense protein BPIFA1 inhibited _C. albicans_ biofilm formation and downregulated several virulence genes [80]. Household larval AMP phormicin C-NS was modified using benzoic and sorbic acid (food preservatives) and inhibited _C. albicans_ bud-to-hyphal transition, as well as biofilm formation [81]. Cnt[15-34], the C-terminal part of the AMP Crotalcidin derived from rattlesnake venom, inhibited biofilm formation by disrupting the plasma membrane of _C. albicans_ reference strains and funcazole-resistant isolates [82]. The sorption venom-derived AMP ToAP2 dose-dependently inhibited the early phase of biofilms (by 60-99.85% at 25-100 uM) [83]. ToAP2 also decreased the viability of mature biofilms but only at 200 uM. Likewise, CGA-N9-C8, an analogue of CGA-N9, also demonstrated strong activity against early phase and established biofilms [84]. Interestingly, this AMP also showed activity against the persister cells of _C. albicans_. Two publications tested AMPs against _Cryptococcus neoformans_, which is frequently detected in immunocompromised individuals and can cause meningitis in HIV infected persons. AMP-17, a novel AMP derived from _Musca domestica_, showed robust activity against both early phase and established biofilms, inhibiting 80% of biofilm formation (BIC80) at concentrations ranging from 16-32 ug/mL (i.e., two-four-fold MIC) and eradicating 80% of the biofilm (BEC80) at concentrations of 64-128 ug/mL, surpassing the efficacy of funconazole [85]. AMP-17 was also found to inhibit yeast-to-hyphal transition and interfered with the adherence of biofilm cells in _C. albicans_. This activity was associated with the mitogen-activated protein kinase (MAPK) pathway and filamentous growth [86]. Snail-derived (_Pomacea poeyana_) AMPs pom-1 and pom-2 reduced the viability of a range of _Candida_ spp., including _C. albicans_, _C. aureus_, and _C. parapsilosis_[87]. AMP analogues from wasp peptide toxins, MK58911-NH2 and MH58911-NH2, showed strong antimicrobial activity against extra- and intracellular _C. neoformans_[88]. However, only MK58911 possessed activity against early phase and established biofilms, in the 1-8 ug/mL range. The well-known AMPs LL-37 and lysozyme showed no activity to _C. tropicalis_ isolates [89].