Coagulase-negative staphylococci, particularly Staphylococcus epidermidis, can be regarded as potential reservoirs of resistance genes for pathogenic strains, e.g., Staphylococcus aureus. The aim of this study was to assess the prevalence of different resistance phenotypes to macrolide, lincosamide, and streptogramins B (MLSB) antibiotics among erythromycin-resistant S. epidermidis, together with the evaluation of genes promoting the following different types of MLSB resistance:ermA, ermB, ermC,msrA, mphC, and linA/A’. Susceptibility to spiramycin was also examined. Among 75 erythromycin-resistantS. epidermidis isolates, the most frequent phenotypes were macrolides and streptogramins B (MSB) and constitutive MLSB (cMLSB). Moreover, all strains with the cMLSB phenotype and the majority of inducible MLSB (iMLSB) isolates were resistant to spiramycin, whereas strains with the MSB phenotype were sensitive to this antibiotic. The D-shape zone of inhibition around the clindamycin disc near the spiramycin disc was found for some spiramycin-resistant strains with the iMLSB phenotype, suggesting an induction of resistance to clindamycin by this 16-membered macrolide. The most frequently isolated gene was ermC, irrespective of the MLSB resistance phenotype, whereas the most often noted gene combination wasermC, mphC, linA/A’. The results obtained showed that the genes responsible for different mechanisms of MLSB resistance in S. epidermidis generally coexist, often without the phenotypic expression of each of them.

Antimicrobial resistance spurred by the overuse and misuse of antibiotics is a major global health concern, and of the Gram positive bacteria, S. aureus is a leading cause of mortality and morbidity. Alternative strategies to treat S. aureus infections, such as combination therapy, are urgently needed. In this study, a checkerboard method was used to evaluate synergistic interactions between nine thiosemicarbazides (4-benzoyl-1-(2,3-dichloro-benzoyl)thiosemicarbazides 1–5 and 4-aryl-1-(2-fluorobenzoyl)thiosemicarbazides 6–9) and conventional antibiotics against S. aureus ATCC 25923, which were determined as the fractional inhibitory concentration indices (FICIs). For these experiments, amoxicillin, gentamicin, levofloxacin, linezolid, and vancomycin were selected to represent the five antimicrobial classes most commonly used in clinical practice. With one exception of 7-vancomycin combination, none of the forty-five thiosemicarbazide-antibiotic combinations tested had an antagonistic effect, showing promising results with respect to a combination therapy. The synergic effect was observed for the 2-linezolid, 4-levofloxacin, 5-linezolid, 6-gentamicin, 6-linezolid, and 7-levofloxacin combinations. No interactions were seen in combination of the thiosemicarbazide with gentamicin or vancomycin, whereas all combinations with linezolid acted in additive or synergism, except for 6-gentamicin and 7-linezolid. The 4-(4-chlorophenyl)-1-(2-fluorobenzoyl)thiosemicarbazide 6 showed a clear preference for the potency; it affected synergistically in combinations with gentamicin or linezolid and additively in combinations with amoxicillin, levofloxacin, or vancomycin. In further studies, the inhibitory potency of the thiosemicarbazides against S. aureus DNA gyrase and topoisomerase IV was examined to clarify the molecular mechanism involved in their synergistic effect in combination with levofloxacin. The most potent synergist 6 at concentration of 100 µM was able to inhibit ~50% activity of S. aureus DNA gyrase, thereby suggesting that its anti-gyrase activity, although weak, may be a possible factor contributing to its synergism effect in combination with linezolid or gentamycin.

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The filamentation ability of Candida albicans represents one of the main virulence factors allowing for host tissue penetration and biofilm formation. The aim of this paper was to study the genetic background of the hyperfilamentous biofilm development in vitro in C. albicans isolated from the oral cavity of a lung cancer patient. Analyzed C. albicans isolates (CA1, CA2, CA3) were chosen based on their different structures of mature biofilm. The CA3 isolate possessing hyperfilamentation properties and forming high biofilm was compared with CA1 and CA2 isolates exhibiting low or average biofilm-forming ability, respectively. The detailed biofilm organization was studied with the use of confocal scanning laser microscopy. The whole transcriptome analysis was conducted during three stages of biofilm development (24 h, 48 h, 72 h). In contrast to CA1 and/or CA2 isolate, the CA3 isolate was characterized by a significant upregulation of genes encoding for cell wall proteins (HWP1, PGA13, PGA44, ALS3) and candidalysin (ECE1), as well as being involved in iron metabolism (FRE1, ALS3), sulfur metabolism (HAL21), the degradation of aromatic compounds (HQD2), and membrane transport (DIP5, PHO89, TNA1). In contrast, some genes (SCW11, FGR41, RBE1) in the CA3 were downregulated. We also observed the overexpression of a few genes over time—mainly FRE1, ATX1, CSA2 involved in iron metabolism. This is the first insight into the potential function of multiple genes in the hyperfilamentous biofilm formation in C. albicans, primarily isolated from host tissue, which may have an important clinical impact on cancer patients. Moreover, the presented data can lay the foundation for further research on novel pathogen-specific targets for antifungal drugs.