LiaX is a surrogate marker for cell envelope stress and daptomycin non-susceptibility in < em > Enterococcus faecium < /em >
Antimicrob Agents Chemother. 2024 Jan 30:e0106923. doi: 10.1128/aac.01069-23. Online ahead of print.ABSTRACTDaptomycin (DAP) is often used as a first-line therapy to treat vancomycin-resistant Enterococcus faecium infections, but emergence of DAP non-susceptibility threatens the effectiveness of this antibiotic. Moreover, current methods to determine DAP minimum inhibitory concentrations (MICs) have poor reproducibility and accuracy. In enterococci, DAP resistance is mediated by the LiaFSR cell membrane stress response system, and deletion of liaR encoding the response regulator results in hypersusceptibility to DAP and an...
Source: Antimicrobial Agents and Chemotherapy - January 30, 2024 Category: Microbiology Authors: Dierdre B Axell-House Shelby R Simar Diana Panesso Sandra Rincon William R Miller Ayesha Khan Orville A Pemberton Lizbet Valdez April H Nguyen Kara S Hood Kirsten Rydell Andrea M DeTranaltes Mary N Jones Rachel Atterstrom Jinnethe Reyes Pranoti V Sahasrab Source Type: research

Transposition mechanism of IS < em > Apl1 < /em > -the determinant of colistin resistance dissemination
In conclusion, the regulation of ISApl1-self-circling is predominantly controlled by the inverted repeat (IR) sequence and the HU protein. This molecular mechanism deepens our comprehension of mcr-1 dissemination.PMID:38289082 | DOI:10.1128/aac.01231-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - January 30, 2024 Category: Microbiology Authors: Wei Li Zhien He Wei Di Weifeng Xu Yujie Li Baolin Sun Source Type: research

< em > In vivo < /em > evaluation of < em > Clostridioides difficile < /em > enoyl-ACP reductase II (FabK) inhibition by phenylimidazole unveils a promising narrow-spectrum antimicrobial strategy
Antimicrob Agents Chemother. 2024 Jan 24:e0122223. doi: 10.1128/aac.01222-23. Online ahead of print.ABSTRACTClostridioides difficile infection (CDI) is a leading cause of hospital-acquired diarrhea, which often stems from disruption of the gut microbiota by broad-spectrum antibiotics. The increasing prevalence of antibiotic-resistant C. difficile strains, combined with disappointing clinical trial results for recent antibiotic candidates, underscores the urgent need for novel CDI antibiotics. To this end, we investigated C. difficile enoyl ACP reductase (CdFabK), a crucial enzyme in de novo fatty acid synthesis, as a drug ...
Source: Antimicrobial Agents and Chemotherapy - January 24, 2024 Category: Microbiology Authors: Chetna Dureja Jacob T Rutherford Fahad B A Pavel Krissada Norseeda Isaac Prah Dianqing Sun Kirk E Hevener Julian G Hurdle Source Type: research

Characterization of the < em > Pneumocystis jirovecii < /em > and < em > Pneumocystis murina < /em > phosphoglucomutases (Pgm2s): a potential target for < em > Pneumocystis < /em > therapy
Antimicrob Agents Chemother. 2024 Jan 23:e0075623. doi: 10.1128/aac.00756-23. Online ahead of print.ABSTRACTPneumocystis cyst life forms contain abundant β-glucan carbohydrates, synthesized using β-1,3 and β-1,6 glucan synthase enzymes and the donor uridine diphosphate (UDP)-glucose. In yeast, phosphoglucomutase (PGM) plays a crucial role in carbohydrate metabolism by interconverting glucose 1-phosphate and glucose 6-phosphate, a vital step in UDP pools for β-glucan cell wall formation. This pathway has not yet been defined in Pneumocystis. Herein, we surveyed the Pneumocystis jirovecii and Pneumocystis murina genomes,...
Source: Antimicrobial Agents and Chemotherapy - January 23, 2024 Category: Microbiology Authors: Theodore J Kottom Eva M Carmona Andrew H Limper Source Type: research

Genetic complexity alters drug susceptibility of asexual and gametocyte stages of < em > Plasmodium falciparum < /em > to antimalarial candidates
In conclusion, this is the first study to investigate the efficacy of antimalarial candidates on both ABS parasites and gametocytes from P. falciparum clinical isolates where the influence of parasite genetic complexity is highlighted, ultimately aiding the malaria elimination agenda.PMID:38259087 | DOI:10.1128/aac.01291-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - January 23, 2024 Category: Microbiology Authors: Nicola Greyling Mari ëtte van der Watt Hazel Gwarinda Ashleigh van Heerden Bryan Greenhouse Didier Leroy Jandeli Niemand Lyn-Mari é Birkholtz Source Type: research

The mechanism of ceftazidime and cefiderocol hydrolysis by D179Y variants of KPC carbapenemases is similar and involves the formation of a long-lived covalent intermediate
Antimicrob Agents Chemother. 2024 Jan 23:e0110823. doi: 10.1128/aac.01108-23. Online ahead of print.ABSTRACTKlebsiella pneumoniae carbapenemase (KPC) variants have been described that confer resistance to both ceftazidime-avibactam and cefiderocol. Of these, KPC-33 and KPC-31 are D179Y-containing variants derived from KPC-2 and KPC-3, respectively. To better understand this atypical phenotype, the catalytic mechanism of ceftazidime and cefiderocol hydrolysis by KPC-33 and KPC-31 as well as the ancestral KPC-2 and KPC-3 enzymes was studied. Steady-state kinetics showed that the D179Y substitution in either KPC-2 or KPC-3 is...
Source: Antimicrobial Agents and Chemotherapy - January 23, 2024 Category: Microbiology Authors: Andre Birgy Christina Nnabuife Timothy Palzkill Source Type: research

Global genetic diversity and Asian clades evolution: a phylogeographic study of < em > Staphylococcus aureus < /em > sequence type 5
This study included 368 ST5 genome sequences, including 111 newly generated sequences. Primary phylogenetic analysis suggested that there are five clades, and geographical clustering of ST5 methicillin-resistant S. aureus (MRSA) was linked to the acquisition of S. aureus pathogenicity islands (SaPIs; enterotoxin gene island) and integration of the prophage φSa3. The most recent common ancestor of global S. aureus ST5 dates back to the mid-1940s, coinciding with the clinical introduction of penicillin. Bayesian phylogeographic inference allowed to ancestrally trace the Asian ST5 MRSA clade to Japan, which may have spread t...
Source: Antimicrobial Agents and Chemotherapy - January 23, 2024 Category: Microbiology Authors: Fengning Chen Yuyao Yin Hongbin Chen Ruobing Wang Shuyi Wang Hui Wang Source Type: research

AgrA directly binds to the promoter of < em > vraSR < /em > and downregulates its expression in < em > Staphylococcus aureus < /em >
In conclusion, our results indicated that the loss of agr function in S. aureus may contribute to the evolution of reduced vancomycin susceptibility through the downregulation of vraSR.PMID:38259090 | DOI:10.1128/aac.00893-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - January 23, 2024 Category: Microbiology Authors: Xueer Liu Yangyan Wang Wenjiao Chang Yuanyuan Dai Xiaoling Ma Source Type: research

Clofazimine as a substitute for rifampicin improves efficacy of < em > Mycobacterium avium < /em > pulmonary disease treatment in the hollow-fiber model
Antimicrob Agents Chemother. 2024 Jan 23:e0115723. doi: 10.1128/aac.01157-23. Online ahead of print.ABSTRACTMycobacterium avium complex pulmonary disease is treated with an azithromycin, ethambutol, and rifampicin regimen, with limited efficacy. The role of rifampicin is controversial due to inactivity, adverse effects, and drug interactions. Here, we evaluated the efficacy of clofazimine as a substitute for rifampicin in an intracellular hollow-fiber infection model. THP-1 cells, which are monocytes isolated from peripheral blood from an acute monocytic leukemia patient, were infected with M. avium ATCC 700898 and exposed...
Source: Antimicrobial Agents and Chemotherapy - January 23, 2024 Category: Microbiology Authors: Sandra Salillas Jelmer Raaijmakers Rob E Aarnoutse Elin M Svensson Khalid Asouit Erik van den Hombergh Lindsey Te Brake Ralf Stemkens Heiman F L Wertheim Wouter Hoefsloot Jakko van Ingen Source Type: research

NorA efflux pump mediates < em > Staphylococcus aureus < /em > response to < em > Pseudomonas aeruginosa < /em > pyocyanin toxicity
Antimicrob Agents Chemother. 2024 Feb 7;68(2):e0100123. doi: 10.1128/aac.01001-23. Epub 2024 Jan 17.ABSTRACTEndogenous transporters protect Staphylococcus aureus against antibiotics and also contribute to bacterial defense from environmental toxins. We evaluated the effect of overexpression of four efflux pumps, NorA, NorB, NorC, and Tet38, on S. aureus survival following exposure to pyocyanin (PYO) of Pseudomonas aeruginosa, using a well diffusion assay. We measured the PYO-created inhibition zone and found that only an overexpression of NorA reduced S. aureus susceptibility to pyocyanin killing. The MICPYO of the NorA ov...
Source: Antimicrobial Agents and Chemotherapy - January 17, 2024 Category: Microbiology Authors: Q C Truong-Bolduc L M Yonker Y Wang B G Lawton D C Hooper Source Type: research

HOCl-producing electrochemical bandage for treating < em > Pseudomonas aeruginosa < /em > -infected murine wounds
In conclusion, an HOCl-producing e-bandage reduced P. aeruginosa in wound biofilms with no impairment in wound healing, representing a promising antibiotic-free approach for addressing wound infection.PMID:38214514 | DOI:10.1128/aac.01216-23 (Source: Antimicrobial Agents and Chemotherapy)
Source: Antimicrobial Agents and Chemotherapy - January 12, 2024 Category: Microbiology Authors: Derek Fleming Ibrahim Bozyel Dilara Ozdemir Judith Alvarez Otero Melissa J Karau Md Monzurul Islam Anoy Christina Koscianski Audrey N Schuetz Kerryl E Greenwood-Quaintance Jayawant N Mandrekar Haluk Beyenal Robin Patel Source Type: research

< em > In vitro < /em > activity of manogepix and comparators against infrequently encountered yeast and mold isolates from the SENTRY Surveillance Program (2017-2022)
This study determined the in vitro activity of manogepix and comparators against a large collection of infrequently encountered yeast and molds. Manogepix demonstrated potent in vitro activity against infrequently encountered yeasts exhibiting elevated MIC values to other drug classes, including Candida spp. (MIC50/90, 0.008/0.12 mg/L), Saprochaete clavata (Magnusiomyces clavatus) (MIC50/90, 0.03/0.06 mg/L), Magnusiomyces capitatus (MICrange, 0.016-0.06 mg/L), Rhodotorula minuta (MIC, 0.016 mg/L), and Rhodotorula mucilaginosa (MIC50/90, 0.03/0.12 mg/L). Similarly, manogepix was active against infrequently encountered mold ...
Source: Antimicrobial Agents and Chemotherapy - January 11, 2024 Category: Microbiology Authors: Michael Pfaller Michael Huband Paul A Bien Cecilia G Carvalhaes Abby Klauer Mariana Castanheira Source Type: research

Nitric oxide-releasing prodrug for the treatment of complex < em > Mycobacterium abscessus < /em > infections
In this report, we evaluate a nitric oxide (NO)-releasing prodrug [methyl tris diazeniumdiolate (MD3)] against a panel of NTM clinical isolates and as a treatment for acute and chronic NTM infections in vivo. Its efficacy in inhibiting growth or killing mycobacteria was explored in vitro alongside evaluation of the impact to primary human airway epithelial tissue. Airway epithelial tissues remained viable after exposure at concentrations of MD3 needed to kill mycobacteria, with no inherent toxic effect from drug scaffold after NO liberation. Resistance studies conducted via serial passage with representative Mycobacterium ...
Source: Antimicrobial Agents and Chemotherapy - January 11, 2024 Category: Microbiology Authors: Rebecca A McDonald Sarah G Nagy Madyson Chambers Chris A Broberg Mona J R Ahonen Mark H Schoenfisch Source Type: research

< em > In vitro < /em > activity of ibrexafungerp against clinically relevant echinocandin-resistant < em > Candida < /em > strains
Antimicrob Agents Chemother. 2024 Feb 7;68(2):e0132423. doi: 10.1128/aac.01324-23. Epub 2024 Jan 11.ABSTRACTInvasive candidiasis is a major hospital-acquired infection. Usually, echinocandins are considered first-line treatment. However, resistant phenotypes have emerged. Ibrexafungerp (IBX) is a new antifungal substance with potent anti-Candida activity. We challenged IBX with a library of 192 pheno-/genotypically echinocandin-resistant Candida isolates, focusing on the substance susceptibility, its activity on certain FKS hotspot (HS) mutated strains, and applying WTULs (wild-type upper limits). Therefore, a 9-year-old s...
Source: Antimicrobial Agents and Chemotherapy - January 11, 2024 Category: Microbiology Authors: Alexander Maximilian Aldejohann Carolina Menner Nadja Thielemann Ronny Martin Grit Walther Oliver Kurzai Source Type: research

Targeting host tyrosine kinase receptor EphA2 signaling via small-molecule ALW-II-41-27 inhibits macrophage pro-inflammatory signaling responses to < em > Pneumocystis carinii < /em > β-glucans
Antimicrob Agents Chemother. 2024 Feb 7;68(2):e0081123. doi: 10.1128/aac.00811-23. Epub 2024 Jan 11.ABSTRACTPneumocystis jirovecii, the fungus that causes Pneumocystis jirovecii pneumonia (PJP), is a leading cause of morbidity and mortality in immunocompromised individuals. We have previously shown that lung epithelial cells can bind Pneumocystis spp. β-glucans via the EphA2 receptor, resulting in activation and release of proinflammatory cytokines. Herein, we show that in vivo Pneumocystis spp. β-glucans activation of the inflammatory signaling cascade in macrophages can be pharmacodynamically inhibited with the EphA2 r...
Source: Antimicrobial Agents and Chemotherapy - January 11, 2024 Category: Microbiology Authors: Theodore J Kottom Eva M Carmona Andrew H Limper Source Type: research