Sterol content and polyene antibiotic resistance in isolates of Candida krusei, Candida parakrusei, and Candida tropicalis

1977 ◽  
Vol 23 (4) ◽  
pp. 398-401 ◽  
Author(s):  
L. M. Safe ◽  
S. H. Safe ◽  
R. E. Subden ◽  
D. C. Morris

Three isolates, one from each species of Candida krusei, C. parakrusei, and C. tropicalis, obtained from infected patients, were more tolerant of significantly higher concentrations of polyene antibiotics than the corresponding reference wild types. The resistant strains isolated had the same sterols as their wild-type counterparts but in lower concentrations.

1977 ◽  
Vol 23 (1) ◽  
pp. 113-115 ◽  
Author(s):  
D. Johnson ◽  
R. Subden

Ergosterol, the principle sterol of many wild-type Neurospora and other Ascomycetes, had a greater affinity for polyene antibiotics than did lichesterol or eburicol, the sterols of some resistant mutant strains. The affinity was demonstrated by comparing the sterols extracted from sensitive and resistant strains of Neurospora crassa and Candida albicans for protection against polyene inhibition of sensitive N. crassa and for their ability to alter specific polyene absorption maxima.


2020 ◽  
Author(s):  
Esmeralda Z. Reyes-Fernández ◽  
Shimon Schuldiner

ABSTRACTAwareness of the problem of antimicrobial resistance (AMR) has escalated, and drug-resistant infections are named among the most urgent issues facing clinicians today. Bacteria can acquire resistance to antibiotics by a variety of mechanisms that, at times, involve changes in their metabolic status, thus altering diverse biochemical reactions, many of them pH-dependent. In this work, we found that modulation of the cytoplasmic pH (pHi) of Escherichia coli provides a thus far unexplored strategy to support resistance. We show here that the acidification of the cytoplasmic pH is a previously unrecognized consequence of the activation of the marRAB operon. The acidification itself contributes to the full implementation of the resistance phenotype. We measured the pHi of two resistant strains, developed in our laboratory, that carry mutations in marR that activate the marRAB operon. The pHi of both strains is lower than that of the wild type strain. Inactivation of the marRAB response in both strains weakens resistance, and pHi increases back to wild type levels. Likewise, we showed that exposure of wild type cells to weak acids that caused acidification of the cytoplasm induced a resistant phenotype, independent of the marRAB response. We speculate that the decrease of the cytoplasmic pH brought about by activation of the marRAB response provides a signaling mechanism that modifies metabolic pathways and serves to cope with stress and to lower metabolic costs.SIGNIFICANCEThe decreasing effectiveness of antibiotics in treating common infections has quickened in recent years, and resistance has spread worldwide. There is an urgent need to understand the mechanisms underlying acquisition and maintenance of resistance, and here we identify a novel element in the chain of events leading to a full-fledged clinically relevant state. The Escherichia coli multiple antibiotic resistance (mar) regulon is induced by a variety of signals and modulates the activity of dozens of target genes involved in resistance to antibiotics. We report here a thus far unidentified result of this activation: acidification of the cytoplasmic pH. Manipulation of the cytoplasmic pH with weak acids and bases, independently of the mar response, shows that the acidification significantly increases resistance.


2021 ◽  
Vol 14 (4) ◽  
pp. 325
Author(s):  
David Sáez Moreno ◽  
Zehra Visram ◽  
Michele Mutti ◽  
Marcela Restrepo-Córdoba ◽  
Susana Hartmann ◽  
...  

Due to the rapid spread of antibiotic resistance, and the difficulties of treating biofilm-associated infections, alternative treatments for S. aureus infections are urgently needed. We tested the lytic activity of several wild type phages against a panel of 110 S. aureus strains (MRSA/MSSA) composed to reflect the prevalence of S. aureus clonal complexes in human infections. The plaquing host ranges (PHR) of the wild type phages were in the range of 51% to 60%. We also measured what we called the kinetic host range (KHR), i.e., the percentage of strains for which growth in suspension was suppressed for 24 h. The KHR of the wild type phages ranged from 2% to 49%, substantially lower than the PHRs. To improve the KHR and other key pharmaceutical properties, we bred the phages by mixing and propagating cocktails on a subset of S. aureus strains. These bred phages, which we termed evolution-squared (ε2) phages, have broader KHRs up to 64% and increased virulence compared to the ancestors. The ε2-phages with the broadest KHR have genomes intercrossed from up to three different ancestors. We composed a cocktail of three ε2-phages with an overall KHR of 92% and PHR of 96% on 110 S. aureus strains and called it PM-399. PM-399 has a lower propensity to resistance formation than the standard of care antibiotics vancomycin, rifampicin, or their combination, and no resistance was observed in laboratory settings (detection limit: 1 cell in 1011). In summary, ε2-phages and, in particular PM-399, are promising candidates for an alternative treatment of S. aureus infections.


2021 ◽  
Vol 14 (6) ◽  
pp. 592
Author(s):  
Pavarish Jantorn ◽  
Hawaree Heemmamad ◽  
Tanawan Soimala ◽  
Saowakon Indoung ◽  
Jongkon Saising ◽  
...  

Staphylococcus pseudintermedius is a zoonotic pathogen that can cause life-threatening infections in animals and humans. The study of methicillin-resistant S. pseudintermedius (MRSP) and its ability to produce biofilms is important to select the most suitable treatment. The prevalence and characteristics of S. pseudintermedius isolated from dogs admitted at the Veterinary Teaching Hospital, Prince of Songkla University, Thailand were assessed. Results showed that 28.30% (15/53) of the isolates were MRSP. Amplification of the mecA gene was observed in 93.33% (14/15) MRSP. Methicillin-resistant strains revealed co-resistant patterns against other antibiotics, including chloramphenicol, clindamycin, tetracycline, clarithromycin, ciprofloxacin, and trimethoprim. In this study, all bacterial isolates produced biofilms, while 90.55% of S. pseudintermedius isolates were strong or moderate biofilm producers. Most (45–60%) of the resistant strains were strong biofilm producers, while the correlation between biofilm production and antibiotic resistance was not statistically significant. This is the first study in southern Thailand to investigate the drug-resistant profile of S. pseudintermedius and its ability to form biofilm. The results will contribute to a better understanding of the emergence and prevalence of antimicrobial resistance in S. pseudintermedius.


1997 ◽  
Vol 41 (12) ◽  
pp. 2616-2620 ◽  
Author(s):  
K De Vreese ◽  
I Van Nerum ◽  
K Vermeire ◽  
J Anné ◽  
E De Clercq

The bicyclams are a new class of anti-human immunodeficiency virus (anti-HIV) compounds targeted at viral entry. From marker rescue experiments, it appears that the envelope gp120 glycoprotein plays an important role in the anti-HIV activity of the bicyclams. Bicyclam-resistant strains contain a number of amino acid changes scattered over the V2 to V5 region of gp120. Experiments aimed at estimating the relative importance of particular amino acid changes with regard to the overall resistance pattern are described. The sequences of some partially bicyclam-resistant virus strains, obtained during the resistance development process, were analyzed, and the corresponding 50% effective concentrations were determined. Selected mutations observed in bicyclam-resistant strains were introduced in the wild-type background by site-directed mutagenesis. In addition, some amino acids were back-mutated to their wild-type counterparts in an otherwise JM3100-resistant strain. The sensitivities of these mutant viruses to bicyclams were determined. Construction of chimeric viruses, carrying the V3 loop of JM3100-resistant virus in a wild-type HIV type 1 HXB2 background, enabled us to investigate the importance of the mutations in the V3 loop of JM3100-resistant virus. From the results described in the report, it can be concluded that single amino acid substitutions do not influence the observed resistance to JM3100. Also, the mutations in the V3 loop are not sufficient to engender even a partially resistant phenotype. We postulate that the overall conformation of gp120 determines the degree of sensitivity or resistance of HIV strains to bicyclams.


2012 ◽  
Vol 56 (8) ◽  
pp. 4146-4153 ◽  
Author(s):  
Zaid Al-Nakeeb ◽  
Ajay Sudan ◽  
Adam R. Jeans ◽  
Lea Gregson ◽  
Joanne Goodwin ◽  
...  

ABSTRACTItraconazole is used for the prevention and treatment of infections caused byAspergillus fumigatus. An understanding of the pharmacodynamics of itraconazole against wild-type and triazole-resistant strains provides a basis for innovative therapeutic strategies for treatment of infections. Anin vitromodel of the human alveolus was used to define the pharmacodynamics of itraconazole. Galactomannan was used as a biomarker. The effect of systemic and airway administration of itraconazole was assessed, as was a combination of itraconazole administered to the airway and systemically administered 5FC. Systemically administered itraconazole against the wild type induced a concentration-dependent decline in galactomannan in the alveolar and endothelial compartments. No exposure-response relationships were apparent for the L98H, M220T, or G138C mutant. The administration of itraconazole to the airway resulted in comparable exposure-response relationships to those observed with systemic therapy. This was achieved without detectable concentrations of drug within the endothelial compartment. The airway administration of itraconazole resulted in a definite but submaximal effect in the endothelial compartment against the L98H mutant. The administration of 5FC resulted in a concentration-dependent decline in galactomannan in both the alveolar and endothelial compartments. The combination of airway administration of itraconazole and systemically administered 5FC was additive. Systemic administration of itraconazole is ineffective against Cyp51 mutants. The airway administration of itraconazole is effective for the treatment of wild-type strains and appears to have some activity against the L98H mutants. Combination with other agents, such as 5FC, may enable the attainment of near-maximal antifungal activity.


2015 ◽  
Vol 112 (23) ◽  
pp. 7273-7278 ◽  
Author(s):  
Michael S. Gilmore ◽  
Marcus Rauch ◽  
Matthew M. Ramsey ◽  
Paul R. Himes ◽  
Sriram Varahan ◽  
...  

Multidrug-resistantEnterococcus faecalispossess numerous mobile elements that encode virulence and antibiotic resistance traits as well as new metabolic pathways, often constituting over one-quarter of the genome. It was of interest to determine how this large accretion of mobile elements affects competitive growth in the gastrointestinal (GI) tract consortium. We unexpectedly observed that the prototype clinical isolate strain V583 was actively killed by GI tract flora, whereas commensal enterococci flourished. It was found that killing of V583 resulted from lethal cross-talk between accumulated mobile elements and that this cross-talk was induced by a heptapeptide pheromone produced by nativeE. faecalispresent in the fecal consortium. These results highlight two important aspects of the evolution of multidrug-resistant enterococci: (i) the accretion of mobile elements inE. faecalisV583 renders it incompatible with commensal strains, and (ii) because of this incompatibility, multidrug-resistant strains sharing features found in V583 cannot coexist with commensal strains. The accumulation of mobile elements in hospital isolates of enterococci can include those that are inherently incompatible with native flora, highlighting the importance of maintaining commensal populations as means of preventing colonization and subsequent infection by multidrug-resistant strains.


Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 885
Author(s):  
Gustavo Di Lallo ◽  
Marco Maria D’Andrea ◽  
Samanta Sennati ◽  
Maria Cristina Thaller ◽  
Luciana Migliore ◽  
...  

The improper use of antibiotics by humans may promote the dissemination of resistance in wildlife. The persistence and spread of acquired antibiotic resistance and human-associated bacteria in the environment, while representing a threat to wildlife, can also be exploited as a tool to monitor the extent of human impact, particularly on endangered animal species. Hence, we investigated both the associated enterobacterial species and the presence of acquired resistance traits in the cloacal microbiota of the critically endangered lesser Antillean iguana (Iguana delicatissima), by comparing two separate populations living in similar climatic conditions but exposed to different anthropic pressures. A combination of techniques, including direct plating, DNA sequencing and antimicrobial susceptibility testing allowed us to characterize the dominant enterobacterial populations, the antibiotic resistant strains and their profiles. A higher frequency of Escherichia coli was found in the samples from the more anthropized site, where multi-drug resistant strains were also isolated. These results confirm how human-associated bacteria as well as their antibiotic-resistance determinants may be transferred to wildlife, which, in turn, may act as a reservoir of antibiotic resistance.


2021 ◽  
Vol 66 (1) ◽  
pp. 42-44
Author(s):  
N. A. Gordinskaya ◽  
E. V. Boriskina ◽  
D. V. Kryazhev

1235 strains of Staphylococci isolated in a multidisciplinary children’s clinic were analyzed. The species and antibiotic resistance of Golden and coagulase-negative Staphylococci were studied. The most frequently identified species were: S. aureus-36.06%, S. epidermidis-23.05%, S. haemolyticus-19.7%, S. hominis-14.03%. Phenotype methicillinsensitive strains had 48.9% of the allocated staphylococci, while metitillinrezistentnykh S. aureus was identified in 25.6%, and coagulase-negative staphylococci methicillinresistant- 63.2 per cent. The frequency of associated resistance to aminoglycosides, fluoroquinolones, macrolides and tetracyclines have metitillinresictant strains 92,7%, 78,3%, 83,4% and 52,05% respectively, resistant Staphylococcus and coagulase-negative staphylococci were similar. The minimum number of resistant strains was found in relation to daptomycin, no strains resistant to vancomycin and linezolid were found. Antibiotic resistance of staphylococci in children’s hospitals is determined by the presence of the mecA gene or sensitivity to cefoxitin and does not depend on the type of strain.


2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Wiley A. Schell ◽  
A. M. Jones ◽  
Katyna Borroto-Esoda ◽  
Barbara D. Alexander

ABSTRACT SCY-078 in vitro activity was determined for 178 isolates of resistant or susceptible Candida albicans, Candida dubliniensis, Candida glabrata, Candida krusei, Candida lusitaniae, and Candida parapsilosis, including 44 Candida isolates with known genotypic (FKS1 or FKS2 mutations), phenotypic, or clinical resistance to echinocandins. Results were compared to those for anidulafungin, caspofungin, micafungin, fluconazole, and voriconazole. SCY-078 was shown to have excellent activity against both wild-type isolates and echinocandin- and azole-resistant isolates of Candida species.


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