Advances in Antibiotic and Antifungal Resistance and Related Alternative Therapies

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 16357

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Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, Mănăştur Street, No. 3/5, Cluj-Napoca, Romania
Interests: antibiotic; public health; bacteria; mechanism; treatment
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Special Issue Information

Dear Colleagues,

Antibiotic and antifungal resistance have become the most important challenges in the field of public health, particularly when treating infections in animals and humans caused by multidrug-resistant strains. The most concerning fact in pathogenic bacterial and fungal growth is their increasing resistance to various groups of antibiotics that are currently used in therapy. This ongoing process represents the most dangerous threat to the effectiveness of existing antibiotics and antifungal substances, and that is why research is needed to find more effective alternative treatments. There is a need for accurate data concerning the constant way in which bacteria evolve and manage to evade drug influence. In this way, more knowledge will be brought to the field concerning the mechanisms of resistance and ways to combat this. This Special Issue is focused on publishing multidisciplinary research that focuses on this complex issue. We encourage the publication of all important and updated results in the field of food microbiology, antibacterial resistance, antifungal resistance, characterization of alternative methods, efficient antimicrobial and antifungal agents, and techniques to develop them.

Prof. Dr. Alexandra Tabaran
Guest Editor

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Keywords

  • antibiotic
  • public health
  • bacteria
  • mechanism
  • treatment

Published Papers (11 papers)

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Research

13 pages, 1906 KiB  
Article
Role of Probiotics in Preventing Carbapenem-Resistant Enterobacteriaceae Colonization in the Intensive Care Unit: Risk Factors and Microbiome Analysis Study
by Jung-Hwan Lee, Jongbeom Shin, Soo-Hyun Park, Boram Cha, Ji-Taek Hong, Don-Haeng Lee and Kye Sook Kwon
Microorganisms 2023, 11(12), 2970; https://doi.org/10.3390/microorganisms11122970 - 12 Dec 2023
Viewed by 932
Abstract
Older patients with multiple comorbidities often necessitate prolonged hospital stays and antibiotic treatment in the intensive care unit (ICU), leading to a rise in multidrug-resistant organisms like carbapenem-resistant Enterobacteriaceae (CRE). This study examined risk factors for carbapenem-resistant Enterobacteriaceae colonization in the ICU and [...] Read more.
Older patients with multiple comorbidities often necessitate prolonged hospital stays and antibiotic treatment in the intensive care unit (ICU), leading to a rise in multidrug-resistant organisms like carbapenem-resistant Enterobacteriaceae (CRE). This study examined risk factors for carbapenem-resistant Enterobacteriaceae colonization in the ICU and assessed probiotics’ preventive role. In this single-center, retrospective study, 9099 ICU patients were tested for stool CRE culture from March 2017 to April 2022. We excluded 136 patients with CRE colonization within one week post-admission and 26 who received probiotics before CRE colonization. Ultimately, 8937 CRE-negative patients were selected. Logistic analysis identified CRE colonization risk factors and evaluated probiotics’ influence, including Saccharomyces boulardii or Lactobacillus rhamnosus, used by 474 patients (5.3%) in the ICU. Compared with data on initial admission, 157 patients (1.7%) had newly discovered CRE colonization before discharge. In a multivariate analysis, coronavirus disease 2019, the ICU, tube feeding, antibiotics such as aminoglycoside, extended-spectrum penicillin, stool vancomycin-resistance enterococci colonization, and chronic kidney disease were significantly associated with de novo CRE infection. However, probiotic use was negatively correlated with CRE infection. Managing risk factors and administering probiotics in the ICU may help prevent CRE colonization; large randomized prospective studies are needed. Full article
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10 pages, 273 KiB  
Communication
Antibiotic Use for Sepsis in Hospitalized Neonates in Botswana: Factors Associated with Guideline-Divergent Prescribing
by Jameson Dowling, Tonya Arscott-Mills, One Bayani, Mickael Boustany, Banno Moorad, Melissa Richard-Greenblatt, Nametso Tlhako, Morgan Zalot, Andrew P. Steenhoff, Alemayehu M. Gezmu, Britt Nakstad, Jonathan Strysko, Susan E. Coffin and Carolyn McGann
Microorganisms 2023, 11(11), 2641; https://doi.org/10.3390/microorganisms11112641 - 27 Oct 2023
Viewed by 1177
Abstract
In low- and middle-income countries, where antimicrobial access may be erratic and neonatal sepsis pathogens are frequently multidrug-resistant, empiric antibiotic prescribing practices may diverge from the World Health Organization (WHO) guidelines. This study examined antibiotic prescribing for neonatal sepsis at a tertiary referral [...] Read more.
In low- and middle-income countries, where antimicrobial access may be erratic and neonatal sepsis pathogens are frequently multidrug-resistant, empiric antibiotic prescribing practices may diverge from the World Health Organization (WHO) guidelines. This study examined antibiotic prescribing for neonatal sepsis at a tertiary referral hospital neonatal unit in Gaborone, Botswana, using data from a prospective cohort of 467 neonates. We reviewed antibiotic prescriptions for the first episode of suspected sepsis, categorized as early-onset (EOS, days 0–3) or late-onset (LOS, >3 days). The WHO prescribing guidelines were used to determine whether antibiotics were “guideline-synchronous” or “guideline-divergent”. Logistic regression models examined independent associations between the time of neonatal sepsis onset and estimated gestational age (EGA) with guideline-divergent antibiotic use. The majority (325/470, 69%) were prescribed one or more antibiotics, and 31 (10%) received guideline-divergent antibiotics. Risk factors for guideline-divergent prescribing included neonates with LOS, compared to EOS (aOR [95% CI]: 4.89 (1.81, 12.57)). Prematurity was a risk factor for guideline-divergent prescribing. Every 1-week decrease in EGA resulted in 11% increased odds of guideline-divergent antibiotics (OR [95% CI]: 0.89 (0.81, 0.97)). Premature infants with LOS had higher odds of guideline-divergent prescribing. Studies are needed to define the causes of this differential rate of guideline-divergent prescribing to guide future interventions. Full article
15 pages, 8839 KiB  
Article
Alpha-Naphthoflavone as a Novel Scaffold for the Design of Potential Inhibitors of the APH(3’)-IIIa Nucleotide-Binding Site of Enterococcus faecalis
by Juliana Carolina Amorim and Juan Marcelo Carpio
Microorganisms 2023, 11(9), 2351; https://doi.org/10.3390/microorganisms11092351 - 20 Sep 2023
Cited by 1 | Viewed by 891
Abstract
The spread of nosocomial infections caused by antibiotic-resistant Enterococcus faecalis is one of the major threats to global health at present. While aminoglycosides are often used to combat these infections, their effectiveness is reduced by various resistance mechanisms, including aminoglycoside modifying enzymes, and [...] Read more.
The spread of nosocomial infections caused by antibiotic-resistant Enterococcus faecalis is one of the major threats to global health at present. While aminoglycosides are often used to combat these infections, their effectiveness is reduced by various resistance mechanisms, including aminoglycoside modifying enzymes, and there are currently no drugs to inhibit these enzymes. To address this issue, this study was conducted to identify potential aminoglycoside adjuvants from a database of 462 flavones. The affinity of these molecules with the nucleotide-binding site (NBS) of aminoglycoside phosphotransferase type IIIa of E. faecalis (EfAPH(3’)-IIIa) was evaluated, and the five molecules with the highest binding energies were identified. Of these, four were naphthoflavones, suggesting that their backbone could be useful in designing potential inhibitors. The highest-ranked naphthoflavone, 2-phenyl-4H-benzo[h]chromen-4-one, was modified to generate two new derivatives (ANF2OHC and ANF2OHCC) to interact with the NBS similarly to adenine in ATP. These derivatives showed higher binding free energies, better stability in molecular dynamics analysis and superior pharmacokinetic and toxicological profiles compared to the parent molecule. These findings suggest that these alpha-naphthoflavone derivatives are potential inhibitors of EfAPH(3’)-IIIa and that this core may be a promising scaffold for developing adjuvants that restore the sensitivity of aminoglycosides. Full article
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16 pages, 2983 KiB  
Article
Genomic Characterization of IMP-Producing Pseudomonas aeruginosa in Bulgaria Reveals the Emergence of IMP-100, a Novel Plasmid-Mediated Variant Coexisting with a Chromosomal VIM-4
by Ivan Stoikov, Ivan N. Ivanov, Deyan Donchev, Deana Teneva, Elina Dobreva, Rumyana Hristova and Stefana Sabtcheva
Microorganisms 2023, 11(9), 2270; https://doi.org/10.3390/microorganisms11092270 - 09 Sep 2023
Viewed by 1271
Abstract
Multidrug-resistant (MDR) Pseudomonas aeruginosa infections represent a major public health concern and require comprehensive understanding of their genetic makeup. This study investigated the first occurrence of imipenemase (IMP)-carrying P. aeruginosa strains from Bulgaria. Whole genome sequencing identified a novel plasmid-mediated IMP-100 allele located [...] Read more.
Multidrug-resistant (MDR) Pseudomonas aeruginosa infections represent a major public health concern and require comprehensive understanding of their genetic makeup. This study investigated the first occurrence of imipenemase (IMP)-carrying P. aeruginosa strains from Bulgaria. Whole genome sequencing identified a novel plasmid-mediated IMP-100 allele located in a a novel In4886 integron embedded in a putative Tn7700 transposon. Two other closely related chromosomal IMP variants, IMP-13 and IMP-84, were also detected. The IMP-producers were resistant to last-line drugs including cefiderocol (CFDC) (two out of three) and susceptible to colistin. The IMP-13/84 cassettes were situated in a In320 integron inserted in a Tn5051-like transposon as previously reported. Lastly, the p4782-IMP plasmid rendered the PA01 transformant resistant to CFDC, suggesting a transferable CFDC resistance. A variety of virulence factors associated with adhesion, antiphagocytosis, iron uptake, and quorum sensing, as well as secretion systems, toxins, and proteases, were confirmed, suggesting significant pathogenic potential consistent with the observed strong biofilm formation. The emergence of IMP-producing MDR P. aeruginosa is alarming as it remains unsusceptible even to last-generation drugs like CFDC. Newly detected IMP-100 was even located in a CFDC-resistant XDR strain. Full article
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12 pages, 999 KiB  
Article
Genome-Wide DNA Changes Acquired by Candida albicans Caspofungin-Adapted Mutants
by Jeffrey Zuber, Sudisht K. Sah, David H. Mathews and Elena Rustchenko
Microorganisms 2023, 11(8), 1870; https://doi.org/10.3390/microorganisms11081870 - 25 Jul 2023
Cited by 1 | Viewed by 790
Abstract
Drugs from the echinocandin (ECN) class are now recommended ‘front-line’ treatments of infections caused by a prevailing fungal pathogen, C. albicans. However, the increased use of ECNs is associated with a rising resistance to ECNs. As the acquisition of ECN resistance in [...] Read more.
Drugs from the echinocandin (ECN) class are now recommended ‘front-line’ treatments of infections caused by a prevailing fungal pathogen, C. albicans. However, the increased use of ECNs is associated with a rising resistance to ECNs. As the acquisition of ECN resistance in C. albicans is viewed as a multistep evolution, determining factors that are associated with the decreased ECN susceptibility is of importance. We have recently identified two cohorts of genes that are either up- or downregulated in concert in order to control remodeling of cell wall, an organelle targeted by ECNs, in laboratory mutants with decreased ECN susceptibility. Here, we profiled the global DNA sequence of four of these adapted mutants in search of DNA changes that are associated with decreased ECN susceptibility. We find a limited number of 112 unique mutations representing two alternative mutational pathways. Approximately half of the mutations occurred as hotspots. Approximately half of mutations and hotspots were shared by ECN-adapted mutants despite the mutants arising as independent events and differing in some of their phenotypes, as well as in condition of chromosome 5. A total of 88 mutations are associated with 43 open reading frames (ORFs) and occurred inside of an ORF or within 1 kb of an ORF, predominantly as single-nucleotide substitution. Mutations occurred more often in the 5′-UTR than in the 3′-UTR by a 1.67:1 ratio. A total of 16 mutations mapped to eight genomic features that were not ORFs: Tca4-4 retrotransposon; Tca2-7 retrotransposon; lambda-4a long terminal repeat; mu-Ra long terminal repeat; MRS-7b Major Repeat Sequence; MRS-R Major Repeat Sequence; RB2-5a repeat sequence; and tL (CAA) leucine tRNA. Finally, eight mutations are not associated with any ORF or other genomic feature. Repeated occurrence of single-nucleotide substitutions in non-related drug-adapted mutants strongly indicates that these DNA changes are accompanying drug adaptation and could possibly influence ECN susceptibility, thus serving as factors facilitating evolution of ECN drug resistance due to classical mutations in FKS1. Full article
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17 pages, 4248 KiB  
Article
Comparative Genomic Analysis of Multi-Drug Resistant Pseudomonas aeruginosa Sequence Type 235 Isolated from Sudan
by Mohamed A. Hussain, Malik Suliman Mohamed, Hisham N. Altayb, Ahmed Osman Mohamed, Ahmed Ashour, Wadah Osman, Asmaa E. Sherif, Kholoud F. Ghazawi, Samar F. Miski, Sabrin R. M. Ibrahim, Gamal A. Mohamed, Ikhlas A. Sindi, Ahmad A. Alshamrani and Abdelaziz Elgaml
Microorganisms 2023, 11(6), 1432; https://doi.org/10.3390/microorganisms11061432 - 29 May 2023
Viewed by 1498
Abstract
Pseudomonas aeruginosa (P. aeruginosa) is known to be associated with resistance to practically all known antibiotics. This is a cross-sectional, descriptive, laboratory-based analytical study in which 200 P. aeruginosa clinical isolates were involved. The DNA of the most resistant isolate was extracted [...] Read more.
Pseudomonas aeruginosa (P. aeruginosa) is known to be associated with resistance to practically all known antibiotics. This is a cross-sectional, descriptive, laboratory-based analytical study in which 200 P. aeruginosa clinical isolates were involved. The DNA of the most resistant isolate was extracted and its whole genome was sequenced, assembled, annotated, and announced, strain typing was ascribed, and it was subjected to comparative genomic analysis with two susceptible strains. The rate of resistance was 77.89%, 25.13%, 21.61%, 18.09%, 5.53%, and 4.52% for piperacillin, gentamicin, ciprofloxacin, ceftazidime, meropenem, and polymyxin B, respectively. Eighteen percent (36) of the tested isolates exhibited a MDR phenotype. The most MDR strain belonged to epidemic sequence type 235. Comparative genomic analysis of the MDR strain (GenBank: MVDK00000000) with two susceptible strains revealed that the core genes were shared by the three genomes but there were accessory genes that were strain-specific, and this MDR genome had a low CG% (64.6%) content. A prophage sequence and one plasmid were detected in the MDR genome, but amazingly, it contained no resistant genes for drugs with antipseudomonal activity and there was no resistant island. In addition, 67 resistant genes were detected, 19 of them were found only in the MDR genome and 48 genes were efflux pumps, and a novel deleterious point mutation (D87G) was detected in the gyrA gene. The novel deleterious mutation in the gyrA gene (D87G) is a known position behind quinolone resistance. Our findings emphasize the importance of adoption of infection control strategies to prevent dissemination of MDR isolates. Full article
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9 pages, 661 KiB  
Article
Prevalence and Characterisation of Clostridium perfringens Isolates in Food-Producing Animals in Romania
by Corina Beres, Liora Colobatiu, Alexandra Tabaran, Romolica Mihaiu and Marian Mihaiu
Microorganisms 2023, 11(6), 1373; https://doi.org/10.3390/microorganisms11061373 - 24 May 2023
Cited by 2 | Viewed by 1733
Abstract
The aim of the current study was to investigate the prevalence of Clostridium perfringens (C. perfringens) recovered from animal faeces, as well as to determine the antimicrobial susceptibility of such isolates. A total of 14 (14/100; 14%) C. perfringens isolates were [...] Read more.
The aim of the current study was to investigate the prevalence of Clostridium perfringens (C. perfringens) recovered from animal faeces, as well as to determine the antimicrobial susceptibility of such isolates. A total of 14 (14/100; 14%) C. perfringens isolates were isolated from the 100 analysed samples (twelve recovered from faecal samples collected from pigs and two from veal calves’ faecal samples). The preponderant genotype was type A, with all isolates being cpa-positive. The most potent antimicrobial agents against C. perfringens proved to be vancomycin, rifampicin and lincomycin. A strong resistance to tetracycline (71.4%), penicillin (64.2%), erythromycin (42.8%) and enrofloxacin (35.7%) was also observed. To the best of our knowledge, this is the first analysis regarding the prevalence, characterization and antimicrobial susceptibility of C. perfringens in food-producing animals in Romania, adding further evidence for the probable role of animals as a source of resistant C. perfringens strains. Full article
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26 pages, 7595 KiB  
Article
Isolation and Molecular Characterization of Indigenous Penicillium chrysogenum/rubens Strain Portfolio for Penicillin V Production
by Amol M. Sawant, Vishwambar D. Navale and Koteswara Rao Vamkudoth
Microorganisms 2023, 11(5), 1132; https://doi.org/10.3390/microorganisms11051132 - 26 Apr 2023
Cited by 1 | Viewed by 3618
Abstract
Beta (β)-lactam antibiotic is an industrially important molecule produced by Penicillium chrysogenum/rubens. Penicillin is a building block for 6-aminopenicillanic acid (6-APA), an important active pharmaceutical intermediate (API) used for semi-synthetic antibiotics biosynthesis. In this investigation, we isolated and identified Penicillium [...] Read more.
Beta (β)-lactam antibiotic is an industrially important molecule produced by Penicillium chrysogenum/rubens. Penicillin is a building block for 6-aminopenicillanic acid (6-APA), an important active pharmaceutical intermediate (API) used for semi-synthetic antibiotics biosynthesis. In this investigation, we isolated and identified Penicillium chrysogenum, P. rubens, P. brocae, P. citrinum, Aspergillus fumigatus, A. sydowii, Talaromyces tratensis, Scopulariopsis brevicaulis, P. oxalicum, and P. dipodomyicola using the internal transcribed spacer (ITS) region and the β-tubulin (BenA) gene for precise species identification from Indian origin. Furthermore, the BenA gene distinguished between complex species of P. chrysogenum and P. rubens to a certain extent which partially failed by the ITS region. In addition, these species were distinguished by metabolic markers profiled by liquid chromatography–high resolution mass spectrometry (LC-HRMS). Secalonic acid, Meleagrin, and Roquefortine C were absent in P. rubens. The crude extract evaluated for PenV production by antibacterial activities by well diffusion method against Staphylococcus aureus NCIM-2079. A high-performance liquid chromatography (HPLC) method was developed for simultaneous detection of 6-APA, phenoxymethyl penicillin (PenV), and phenoxyacetic acid (POA). The pivotal objective was the development of an indigenous strain portfolio for PenV production. Here, a library of 80 strains of P. chrysogenum/rubens was screened for PenV production. Results showed 28 strains capable of producing PenV in a range from 10 to 120 mg/L when 80 strains were screened for its production. In addition, fermentation parameters, precursor concentration, incubation period, inoculum size, pH, and temperature were monitored for the improved PenV production using promising P. rubens strain BIONCL P45. In conclusion, P. chrysogenum/rubens strains can be explored for the industrial-scale PenV production. Full article
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14 pages, 466 KiB  
Article
Synthesis of Novel Benzenesulfonamide-Bearing Functionalized Imidazole Derivatives as Novel Candidates Targeting Multidrug-Resistant Mycobacterium abscessus Complex
by Benas Balandis, Povilas Kavaliauskas, Birutė Grybaitė, Vidmantas Petraitis, Rūta Petraitienė, Ethan Naing, Andrew Garcia, Ramunė Grigalevičiūtė and Vytautas Mickevičius
Microorganisms 2023, 11(4), 935; https://doi.org/10.3390/microorganisms11040935 - 03 Apr 2023
Cited by 2 | Viewed by 1325
Abstract
Infections caused by drug-resistant (DR) Mycobacterium abscessus (M. abscessus) complex (MAC) are an important public health concern, particularly when affecting individuals with various immunodeficiencies or chronic pulmonary diseases. Rapidly growing antimicrobial resistance among MAC urges us to develop novel antimicrobial candidates [...] Read more.
Infections caused by drug-resistant (DR) Mycobacterium abscessus (M. abscessus) complex (MAC) are an important public health concern, particularly when affecting individuals with various immunodeficiencies or chronic pulmonary diseases. Rapidly growing antimicrobial resistance among MAC urges us to develop novel antimicrobial candidates for future optimization. Therefore, we have designed and synthesized benzenesulfonamide-bearing functionalized imidazole or S-alkylated derivatives and evaluated their antimicrobial activity using multidrug-resistant M. abscessus strains and compared their antimycobacterial activity using M. bovis BCG and M. tuberculosis H37Ra. Benzenesulfonamide-bearing imidazole-2-thiol compound 13, containing 4-CF3 substituent in benzene ring, showed strong antimicrobial activity against the tested mycobacterial strains and was more active than some antibiotics used as a reference. Furthermore, an imidazole-bearing 4-F substituent and S-methyl group demonstrated good antimicrobial activity against M. abscessus complex strains, as well as M. bovis BCG and M. tuberculosis H37Ra. In summary, these results demonstrated that novel benzenesulfonamide derivatives, bearing substituted imidazoles, could be further explored as potential candidates for the further hit-to-lead optimization of novel antimycobacterial compounds. Full article
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10 pages, 1588 KiB  
Article
The Hormetic Effect Observed for Benzalkonium Chloride and Didecyldimethylammonium Chloride in Serratia sp. HRI
by Samantha J. McCarlie, Laurinda Steyn, Louis L. du Preez, Charlotte E. Boucher, Julio Castillo Hernandez and Robert R. Bragg
Microorganisms 2023, 11(3), 564; https://doi.org/10.3390/microorganisms11030564 - 23 Feb 2023
Viewed by 1160
Abstract
Hormesis, or the hormetic effect, is a dose- or concentration-dependent response characterised by growth stimulation at low concentrations and inhibition at high concentrations. The impact of sub-lethal levels of disinfectants on the growth of Serratia species is critical to understanding the increasing number [...] Read more.
Hormesis, or the hormetic effect, is a dose- or concentration-dependent response characterised by growth stimulation at low concentrations and inhibition at high concentrations. The impact of sub-lethal levels of disinfectants on the growth of Serratia species is critical to understanding the increasing number of outbreaks caused by this pathogen in healthcare settings. Serratia sp. HRI and Serratia marcescens ATCC 13880 were cultivated in sub-lethal levels of benzalkonium chloride (BAC), Didecyldimethylammonium chloride (DDAC), and VirukillTM. The maximum specific growth rates, doubling times, and cell counts were compared. The results revealed significant increases in maximum specific growth rates and shorter doubling times for Serratia sp. HRI when cultivated in sub-lethal levels of BAC and DDAC. The significant stimulatory effect of sub-lethal levels of these disinfectants for Serratia sp. HRI represents the first time hormesis has been observed in a Gram-negative bacterium for any disinfectant. Furthermore, this study is the first to observe the hormetic effect after treatment with DDAC and the second study to date analysing the impact of sub-lethal levels of disinfectants on the growth of bacterial species. Full article
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11 pages, 1802 KiB  
Article
Candida albicans Strains Adapted to Caspofungin Due to Aneuploidy Become Highly Tolerant under Continued Drug Pressure
by Farha Husain, Anshuman Yadav, Sudisht K. Sah, Jeffrey J. Hayes and Elena Rustchenko
Microorganisms 2023, 11(1), 23; https://doi.org/10.3390/microorganisms11010023 - 21 Dec 2022
Cited by 3 | Viewed by 1368
Abstract
Candida albicans is a prevalent fungal pathogen of humans. Understanding the development of decreased susceptibility to ECN drugs of this microbe is of substantial interest, as it is viewed as an intermediate step allowing the formation of FKS1 resistance mutations. We used six [...] Read more.
Candida albicans is a prevalent fungal pathogen of humans. Understanding the development of decreased susceptibility to ECN drugs of this microbe is of substantial interest, as it is viewed as an intermediate step allowing the formation of FKS1 resistance mutations. We used six previously characterized mutants that decreased caspofungin susceptibility either by acquiring aneuploidy of chromosome 5 (Ch5) or by aneuploidy-independent mechanisms. When we exposed these caspofungin-adapted mutants to caspofungin again, we obtained 60 evolved mutants with further decreases in caspofungin susceptibility, as determined with CLSI method. We show that the initial adaptation to caspofungin is coupled with the adaptation to other ECNs, such as micafungin and anidulafungin, in mutants with no ploidy change, but not in aneuploid mutants, which become more susceptible to micafungin and anidulafungin. Furthermore, we find that the initial mechanism of caspofungin adaptation determines the pattern of further adaptation as parentals with no ploidy change further adapt to all ECNs by relatively small decreases in susceptibility, whereas aneuploid parentals adapt to all ECNs, primarily by large decrease in susceptibilities. Our data suggest that either distinct or common mechanisms can govern adaptation to different ECNs. Full article
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