Lasioglossins LLIII affect the morphogenesis of Candida albicans and reduces the duration of experimental vaginal candidiasis in mice

Abstract

Lasioglossins are a group of peptides with identified antimicrobial activity. The inhibitory effects of two synthetic lasioglossin derivatives, LLIII and D-isomeric variant LLIII-D, on morphological changes in Candida albicans in vitro and the effect of local administration of LLIII during experimental murine candidiasis were investigated. C. albicans blastoconidia were grown in the presence of lasioglossin LLIII or LLIII-D at concentrations of 11.5 μM and 21 μM, respectively, for 1, 2 and 3 days and their viability determined by flow cytometry using eosin Y staining. Morphological changes were examined by light and fluorescent microscopy. The Candida-inhibitory effect of daily intravaginal administration of 0.7 or 1.4 μg of LLIII was assessed in mice with experimentally-induced vaginal candidiasis. LLIII and LLIII-D lasioglossins exhibited candidacidal activity in vitro (>76% after 24 hr and >84% after 48 hr of incubation). After 72 hr incubation of Candida with low concentration of lasioglossins, an increase in viability was detected, probably due to a Candida antimicrobial peptides evasion strategy. Furthermore, lasioglossins inhibited temperature-induced morphotype changes toward hyphae and pseudohyphae with sporadic occurrence of atypical cells with two or enlarged nuclei, suggesting interference with mitosis or cytokinesis. Local application of LLIII reduced the duration of experimental candidiasis with no evidence of adverse effects. Lasioglossin LLIII is a promising candidate for development as an antimicrobial drug for treating the vaginal candidiasis.

Pathogen-induced tissue-resident memory T H 17 (T RM 17) cells amplify autoimmune kidney disease

“…Other pathogens that infect the human kidney are uropathogenic Escherichia coli strains and Candida albicans. We infected mice with uropathogenic E. coli, which induces a transient form of acute pyelonephritis (56), and with C. albicans, a well-known trigger of T H 17 cell response (57). Analysis after clearance of the renal infections revealed that both pathogens induced T RM 17 cell formation in the kidneys of mice (fig.…”

Perturbation of liquid droplets of P-granule protein LAF-1 by the antimicrobial peptide LL-III

“…10 In this context, the peptide LL-III, extracted from the venom of the eusocial bee Lasioglossum laticeps, showed a remarkable activity against several bacterial strains (both Grampositive and Gram-negative), fungi and cancer cells, coupled with a moderate cytotoxicity which renders this peptide a good candidate for pharmacological applications. 11 The LL-III is a positively charged (+6 at pH 7.4), unstructured peptide composed of 15 amino acids, half of which are hydrophobic residues and half are polar (with five Lys residues). Even if its mode of action is still largely unknown, it was demonstrated that LL-III is able to translocate across the membrane of some cancer cells, localizing mainly in the nucleolus and in granules that are formed through LLPS of proteins and/or nucleic acids.…”

Machine Learning Guided Discovery of Non‐Hemolytic Membrane Disruptive Anticancer Peptides

“…For our second approach, we aimed to select non‐hemolytic ACPs directly. In view of the sparsity of training data for non‐hemolytic ACPs, we focused on LL‐III due to its short length (15 residues) and documented non‐hemolytic ACP activity below 200 μM [39,42–44] . To generate LL–III analogs, we used PDGA [38] with the molecular fingerprint MAP4 as similarity measure.…”

“…In view of the sparsity of training data for nonhemolytic ACPs, we focused on LL-III due to its short length (15 residues) and documented non-hemolytic ACP activity below 200 μM. [39,[42][43][44] To generate LL-III analogs, we used PDGA [38] with the molecular fingerprint MAP4 as similarity measure. This fingerprint is well-suited for virtual screening of molecules of any size range including peptides.…”