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2145. Antagonistic Activity of Lacticseibacillus rhamnosus R3 Against Carbapenem-Resistant Acinetobacter baumannii Strain: A Promising Therapeutic Alternative

BACKGROUND: Acinetobacter baumannii (AB) is a recognized nosocomial pathogen of critical importance Most circulating AB strains are carbapenem-resistant (CRAB), which severely complicates therapeutics with available antibiotics. Probiotic lactic acid bacteria constitute a promising therapeutic alter...

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Autores principales: Rodriguez, Cecilia, Ramlaoui, Dema, Georgeos, Nardin, Gasca, Briea, Leal, Camila, Salzameda, Nicholas, Bonomo, Robert A, Raya, Raul, Ramirez, Maria Soledad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10677412/
http://dx.doi.org/10.1093/ofid/ofad500.1768
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author Rodriguez, Cecilia
Ramlaoui, Dema
Georgeos, Nardin
Gasca, Briea
Leal, Camila
Salzameda, Nicholas
Bonomo, Robert A
Raya, Raul
Ramirez, Maria Soledad
author_facet Rodriguez, Cecilia
Ramlaoui, Dema
Georgeos, Nardin
Gasca, Briea
Leal, Camila
Salzameda, Nicholas
Bonomo, Robert A
Raya, Raul
Ramirez, Maria Soledad
author_sort Rodriguez, Cecilia
collection PubMed
description BACKGROUND: Acinetobacter baumannii (AB) is a recognized nosocomial pathogen of critical importance Most circulating AB strains are carbapenem-resistant (CRAB), which severely complicates therapeutics with available antibiotics. Probiotic lactic acid bacteria constitute a promising therapeutic alternative. Previously, we determined that Lacticaseibacillus rhamnosus R3 (LR-R3) exerts a strong inhibitory capacity on the model strain A118 (susceptible to antibiotics). In this analysis, the antimicrobial activity of LR-R3 against type CRAB hypervirulent strain AB5075 was evaluated. Figure 1 [Figure: see text] A) Transwell migration assay. AB5075 viability after 24h exposure to LR-R3 CFCM. B) CFCM activity obtained from 96h culture of LR-R3 on CRAB strains. METHODS: The inhibitory activity of cell pellet and its cell-free supernatants (CFCM) were determined, respectively, by the soft-agar overlay method, CFCM activity, and transwell migration assay. Also, killing assays and scanning microscopy imaging were performed under co-culture conditions. Lastly, AB5075 transcriptional response when exposed to LR-R3 was assessed by RT-qPCR. RESULTS: The lactic acid bacteria LR-R3 demonstrated a strong inhibitory capacity on AB5075 strain (inhibition halo diameter, DHI >20 mm), with loss of cell viability at 4h of co-culture conditions. The CFCM of LR-R3 also showed similar antimicrobial activity on AB5075 (Fig 1A) and against others CRAB strains (Fig 1B), suggesting that the inhibitory effect observed is due to the presence of a compound or metabolite produced and secreted by the lactobacillus. Microscopy images showed increase formation of outer membrane vesicles (OMVs) and the presence of nanotubes. In addition, significant changes in the expression levels of the studied genes were observed in AB5075 in co-culture with LR-R3: increase in the expression of genes involved in biofilm (csuAB, csuB, ompA); and decrease in the expression of genes involved in the synthesis and utilization of iron (bauA, exbD, bfnA, basE, pirA), and genes related to fatty acid and lipid metabolism (paaA, paaB). CONCLUSION: The results obtained allowed the identification of Lcb. rhamnosus R3 as a probiotic strain with antagonistic activity on the nosocomial pathogen A. baumannii. In addition, it was shown that LR-R3 alters iron and fatty acid metabolism, by virtue of this interaction. This work constitutes the basis for future studies necessary to elucidate the mechanism involved. DISCLOSURES: Robert A. bonomo, MD, Entasis, Merck, VenatoRx, Wockhardt: Grant/Research Support
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spelling pubmed-106774122023-11-27 2145. Antagonistic Activity of Lacticseibacillus rhamnosus R3 Against Carbapenem-Resistant Acinetobacter baumannii Strain: A Promising Therapeutic Alternative Rodriguez, Cecilia Ramlaoui, Dema Georgeos, Nardin Gasca, Briea Leal, Camila Salzameda, Nicholas Bonomo, Robert A Raya, Raul Ramirez, Maria Soledad Open Forum Infect Dis Abstract BACKGROUND: Acinetobacter baumannii (AB) is a recognized nosocomial pathogen of critical importance Most circulating AB strains are carbapenem-resistant (CRAB), which severely complicates therapeutics with available antibiotics. Probiotic lactic acid bacteria constitute a promising therapeutic alternative. Previously, we determined that Lacticaseibacillus rhamnosus R3 (LR-R3) exerts a strong inhibitory capacity on the model strain A118 (susceptible to antibiotics). In this analysis, the antimicrobial activity of LR-R3 against type CRAB hypervirulent strain AB5075 was evaluated. Figure 1 [Figure: see text] A) Transwell migration assay. AB5075 viability after 24h exposure to LR-R3 CFCM. B) CFCM activity obtained from 96h culture of LR-R3 on CRAB strains. METHODS: The inhibitory activity of cell pellet and its cell-free supernatants (CFCM) were determined, respectively, by the soft-agar overlay method, CFCM activity, and transwell migration assay. Also, killing assays and scanning microscopy imaging were performed under co-culture conditions. Lastly, AB5075 transcriptional response when exposed to LR-R3 was assessed by RT-qPCR. RESULTS: The lactic acid bacteria LR-R3 demonstrated a strong inhibitory capacity on AB5075 strain (inhibition halo diameter, DHI >20 mm), with loss of cell viability at 4h of co-culture conditions. The CFCM of LR-R3 also showed similar antimicrobial activity on AB5075 (Fig 1A) and against others CRAB strains (Fig 1B), suggesting that the inhibitory effect observed is due to the presence of a compound or metabolite produced and secreted by the lactobacillus. Microscopy images showed increase formation of outer membrane vesicles (OMVs) and the presence of nanotubes. In addition, significant changes in the expression levels of the studied genes were observed in AB5075 in co-culture with LR-R3: increase in the expression of genes involved in biofilm (csuAB, csuB, ompA); and decrease in the expression of genes involved in the synthesis and utilization of iron (bauA, exbD, bfnA, basE, pirA), and genes related to fatty acid and lipid metabolism (paaA, paaB). CONCLUSION: The results obtained allowed the identification of Lcb. rhamnosus R3 as a probiotic strain with antagonistic activity on the nosocomial pathogen A. baumannii. In addition, it was shown that LR-R3 alters iron and fatty acid metabolism, by virtue of this interaction. This work constitutes the basis for future studies necessary to elucidate the mechanism involved. DISCLOSURES: Robert A. bonomo, MD, Entasis, Merck, VenatoRx, Wockhardt: Grant/Research Support Oxford University Press 2023-11-27 /pmc/articles/PMC10677412/ http://dx.doi.org/10.1093/ofid/ofad500.1768 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Abstract
Rodriguez, Cecilia
Ramlaoui, Dema
Georgeos, Nardin
Gasca, Briea
Leal, Camila
Salzameda, Nicholas
Bonomo, Robert A
Raya, Raul
Ramirez, Maria Soledad
2145. Antagonistic Activity of Lacticseibacillus rhamnosus R3 Against Carbapenem-Resistant Acinetobacter baumannii Strain: A Promising Therapeutic Alternative
title 2145. Antagonistic Activity of Lacticseibacillus rhamnosus R3 Against Carbapenem-Resistant Acinetobacter baumannii Strain: A Promising Therapeutic Alternative
title_full 2145. Antagonistic Activity of Lacticseibacillus rhamnosus R3 Against Carbapenem-Resistant Acinetobacter baumannii Strain: A Promising Therapeutic Alternative
title_fullStr 2145. Antagonistic Activity of Lacticseibacillus rhamnosus R3 Against Carbapenem-Resistant Acinetobacter baumannii Strain: A Promising Therapeutic Alternative
title_full_unstemmed 2145. Antagonistic Activity of Lacticseibacillus rhamnosus R3 Against Carbapenem-Resistant Acinetobacter baumannii Strain: A Promising Therapeutic Alternative
title_short 2145. Antagonistic Activity of Lacticseibacillus rhamnosus R3 Against Carbapenem-Resistant Acinetobacter baumannii Strain: A Promising Therapeutic Alternative
title_sort 2145. antagonistic activity of lacticseibacillus rhamnosus r3 against carbapenem-resistant acinetobacter baumannii strain: a promising therapeutic alternative
topic Abstract
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10677412/
http://dx.doi.org/10.1093/ofid/ofad500.1768
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