Human Serum Proteins and Susceptibility of <i>Acinetobacter baumannii</i> to Cefiderocol: Role of Iron Transport
Cefiderocol, a recently introduced antibiotic, has a chemical structure that includes a cephalosporin that targets cell wall synthesis and a chlorocatechol siderophore moiety that facilitates cell penetration by active iron transporters. Analysis of the effect that human serum, human serum albumin,...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/3/600 |
| _version_ | 1827649913751601152 |
|---|---|
| author | Casin Le Camila Pimentel Fernando Pasteran Marisel R. Tuttobene Tomás Subils Jenny Escalante Brent Nishimura Susana Arriaga Aimee Carranza Vyanka Mezcord Alejandro J. Vila Alejandra Corso Luis A. Actis Marcelo E. Tolmasky Robert A. Bonomo Maria Soledad Ramírez |
| author_facet | Casin Le Camila Pimentel Fernando Pasteran Marisel R. Tuttobene Tomás Subils Jenny Escalante Brent Nishimura Susana Arriaga Aimee Carranza Vyanka Mezcord Alejandro J. Vila Alejandra Corso Luis A. Actis Marcelo E. Tolmasky Robert A. Bonomo Maria Soledad Ramírez |
| author_sort | Casin Le |
| collection | DOAJ |
| description | Cefiderocol, a recently introduced antibiotic, has a chemical structure that includes a cephalosporin that targets cell wall synthesis and a chlorocatechol siderophore moiety that facilitates cell penetration by active iron transporters. Analysis of the effect that human serum, human serum albumin, and human pleural fluid had on growing <i>Acinetobacter baumannii</i> showed that genes related to iron uptake were down-regulated. At the same time, β-lactamase genes were expressed at higher levels. The minimum inhibitory concentrations of this antimicrobial in <i>A. baumannii</i> cells growing in the presence of human serum, human serum albumin, or human pleural fluid were higher than those measured when these fluids were absent from the culture medium. These results correlate with increased expression levels of β-lactamase genes and the down-regulation of iron uptake-related genes in cultures containing human serum, human serum albumin, or human pleural fluid. These modifications in gene expression could explain the less-than-ideal clinical response observed in patients with pulmonary or bloodstream <i>A. baumannii</i> infections. The exposure of the infecting cells to the host’s fluids could cause reduced cefiderocol transport capabilities and increased resistance to β-lactams. The regulation of genes that could impact the <i>A. baumannii</i> susceptibility to cefiderocol, or other antibacterials, is an understudied phenomenon that merits further investigation. |
| first_indexed | 2024-03-09T20:06:15Z |
| format | Article |
| id | doaj.art-d2517f190dfe45c2851f4b1870fb8eb5 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T20:06:15Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-d2517f190dfe45c2851f4b1870fb8eb52023-11-24T00:32:34ZengMDPI AGBiomedicines2227-90592022-03-0110360010.3390/biomedicines10030600Human Serum Proteins and Susceptibility of <i>Acinetobacter baumannii</i> to Cefiderocol: Role of Iron TransportCasin Le0Camila Pimentel1Fernando Pasteran2Marisel R. Tuttobene3Tomás Subils4Jenny Escalante5Brent Nishimura6Susana Arriaga7Aimee Carranza8Vyanka Mezcord9Alejandro J. Vila10Alejandra Corso11Luis A. Actis12Marcelo E. Tolmasky13Robert A. Bonomo14Maria Soledad Ramírez15Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831, USACenter for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831, USANational/Regional Reference Laboratory for Antimicrobial Resistance (NRL), Servicio Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS Dr. Carlos G. Malbrán, Buenos Aires C1282, ArgentinaÁrea Biología Molecular, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario S2000, ArgentinaInstituto de Procesos Biotecnológicos y Químicos de Rosario (IPROBYQ, CONICET-UNR), Rosario S2002, ArgentinaCenter for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831, USACenter for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831, USACenter for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831, USACenter for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831, USACenter for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831, USAInstituto de Biología Molecular y Celular de Rosario (IBR, CONICET-UNR), Rosario S2000, ArgentinaNational/Regional Reference Laboratory for Antimicrobial Resistance (NRL), Servicio Antimicrobianos, Instituto Nacional de Enfermedades Infecciosas, ANLIS Dr. Carlos G. Malbrán, Buenos Aires C1282, ArgentinaDepartment of Microbiology, Miami University, Oxford, OH 45056, USACenter for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831, USADepartments of Medicine, Pharmacology, Molecular Biology and Microbiology, Biochemistry, Proteomics and Bioinformatics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USACenter for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92831, USACefiderocol, a recently introduced antibiotic, has a chemical structure that includes a cephalosporin that targets cell wall synthesis and a chlorocatechol siderophore moiety that facilitates cell penetration by active iron transporters. Analysis of the effect that human serum, human serum albumin, and human pleural fluid had on growing <i>Acinetobacter baumannii</i> showed that genes related to iron uptake were down-regulated. At the same time, β-lactamase genes were expressed at higher levels. The minimum inhibitory concentrations of this antimicrobial in <i>A. baumannii</i> cells growing in the presence of human serum, human serum albumin, or human pleural fluid were higher than those measured when these fluids were absent from the culture medium. These results correlate with increased expression levels of β-lactamase genes and the down-regulation of iron uptake-related genes in cultures containing human serum, human serum albumin, or human pleural fluid. These modifications in gene expression could explain the less-than-ideal clinical response observed in patients with pulmonary or bloodstream <i>A. baumannii</i> infections. The exposure of the infecting cells to the host’s fluids could cause reduced cefiderocol transport capabilities and increased resistance to β-lactams. The regulation of genes that could impact the <i>A. baumannii</i> susceptibility to cefiderocol, or other antibacterials, is an understudied phenomenon that merits further investigation.https://www.mdpi.com/2227-9059/10/3/600<i>Acinetobacter baumannii</i>cefiderocolhuman fluidsironhuman serum albumin |
| spellingShingle | Casin Le Camila Pimentel Fernando Pasteran Marisel R. Tuttobene Tomás Subils Jenny Escalante Brent Nishimura Susana Arriaga Aimee Carranza Vyanka Mezcord Alejandro J. Vila Alejandra Corso Luis A. Actis Marcelo E. Tolmasky Robert A. Bonomo Maria Soledad Ramírez Human Serum Proteins and Susceptibility of <i>Acinetobacter baumannii</i> to Cefiderocol: Role of Iron Transport Biomedicines <i>Acinetobacter baumannii</i> cefiderocol human fluids iron human serum albumin |
| title | Human Serum Proteins and Susceptibility of <i>Acinetobacter baumannii</i> to Cefiderocol: Role of Iron Transport |
| title_full | Human Serum Proteins and Susceptibility of <i>Acinetobacter baumannii</i> to Cefiderocol: Role of Iron Transport |
| title_fullStr | Human Serum Proteins and Susceptibility of <i>Acinetobacter baumannii</i> to Cefiderocol: Role of Iron Transport |
| title_full_unstemmed | Human Serum Proteins and Susceptibility of <i>Acinetobacter baumannii</i> to Cefiderocol: Role of Iron Transport |
| title_short | Human Serum Proteins and Susceptibility of <i>Acinetobacter baumannii</i> to Cefiderocol: Role of Iron Transport |
| title_sort | human serum proteins and susceptibility of i acinetobacter baumannii i to cefiderocol role of iron transport |
| topic | <i>Acinetobacter baumannii</i> cefiderocol human fluids iron human serum albumin |
| url | https://www.mdpi.com/2227-9059/10/3/600 |
| work_keys_str_mv | AT casinle humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT camilapimentel humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT fernandopasteran humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT mariselrtuttobene humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT tomassubils humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT jennyescalante humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT brentnishimura humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT susanaarriaga humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT aimeecarranza humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT vyankamezcord humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT alejandrojvila humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT alejandracorso humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT luisaactis humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT marceloetolmasky humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT robertabonomo humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport AT mariasoledadramirez humanserumproteinsandsusceptibilityofiacinetobacterbaumanniiitocefiderocolroleofirontransport |