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Fighting resistance with redundancy: a path forward for treating antimicrobial-resistant infections?
(American Society for Microbiology, 2025-04-02)
MUNITA SEPULVEDA, JOSE MANUEL
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Pranita D. Tamma
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Cesar A. Arias
Acinetobacter baumannii</jats:italic> (CRAB) remains a major threat, with high mortality and limited effective treatments. Sulbactam-durlobactam has emerged as a promising therapy against CRAB. Sulbactam-durlobactam was combined with imipenem-cilastatin in a clinical trial that led to its United States Food and Drug Administration approval. However, the additive benefit of imipenem remains uncertain. In a recent study (Antimicrob Agents Chemother 69:e01627-24, 2025, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://doi.org/10.1128/aac.01627-24" xlink:type="simple">https://doi.org/10.1128/aac.01627-24</jats:ext-link> ), Veeraraghavan and colleagues provide convincing mechanistic evidence that adding imipenem to sulbactam-durlobactam enhances bacterial killing, likely through complementary inhibition of penicillin binding proteins, leveraging the concept of target redundancy.
Scopus© Citations 2 2
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Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival
(Springer Science and Business Media LLC, 2025-01-18)
Bárbara Mora-Lagos
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María Elena Reyes
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LOBOS GONZALEZ, LORENA DE LOURDES
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Matías del Campo
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Kurt Buchegger
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Gastric cancer (GC) is a significant cancer-related cause of death worldwide. GC’s most used chemotherapeutic regimen is based on platinum drugs such as cisplatin (CDDP). However, CDDP chemoresistance reduces the survival rate of advanced GC. The immune C-C chemokine receptor type 5 (CCR5) have been proposed as a pivotal factor in cancer progression since its blockade has been linked with antineoplastic effects on tumor cell proliferation; nevertheless, its role in the chemoresistance of GC has not been elucidated. This study aimed to determine the effects induced by the CCR5 using Maraviroc (MVC), a highly selective CCR5 antagonist, on CDDP-resistant AGS cells (AGS R-CDDP), tumoroids (<jats:italic>3D</jats:italic> tumor spheroids), and animal models.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>The combined CDDP and MVC treatment reduced cell viability and inhibited tumoroid formation in AGS R-CDDP cells. The effects of the MVC/CDDP combination on apoptosis and cell cycle progression were correlated with the increase in CDDP (dose-dependent). The mRNA levels of C-C Motif Chemokine Ligand 5 (CCL5), the main ligand for CCR5, decreased significantly in cells treated with the MVC/CDDP combination. MVC in the MVC/CDDP combination improved the survival rate and biochemical parameters of CDDP-treated mice by reducing the side effects of CDDP alone.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>This finding suggests that MVC/CDDP combination could be a potential complementary therapy for GC.</jats:p> </jats:sec>
3Scopus© Citations 4
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Editorial: Immune response to gram-negative bacteria in the lungs
(2024)
Agnes Jara-Collao
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POLI HARLOWE, MARIA CECILIA BERTA
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William Bain
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Hernán F. Peñaloza
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ADAR-Mediated A>I(G) RNA Editing in the Genotoxic Drug Response of Breast Cancer
(2024)
Yanara A. Bernal
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Eduardo Durán
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Isidora Solar
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Eduardo A. Sagredo
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ARMISEN YAÑEZ, RICARDO AMADO
<jats:p>Epitranscriptomics is a field that delves into post-transcriptional changes. Among these modifications, the conversion of adenosine to inosine, traduced as guanosine (A>I(G)), is one of the known RNA-editing mechanisms, catalyzed by ADARs. This type of RNA editing is the most common type of editing in mammals and contributes to biological diversity. Disruption in the A>I(G) RNA-editing balance has been linked to diseases, including several types of cancer. Drug resistance in patients with cancer represents a significant public health concern, contributing to increased mortality rates resulting from therapy non-responsiveness and disease progression, representing the greatest challenge for researchers in this field. The A>I(G) RNA editing is involved in several mechanisms over the immunotherapy and genotoxic drug response and drug resistance. This review investigates the relationship between ADAR1 and specific A>I(G) RNA-edited sites, focusing particularly on breast cancer, and the impact of these sites on DNA damage repair and the immune response over anti-cancer therapy. We address the underlying mechanisms, bioinformatics, and in vitro strategies for the identification and validation of A>I(G) RNA-edited sites. We gathered databases related to A>I(G) RNA editing and cancer and discussed the potential clinical and research implications of understanding A>I(G) RNA-editing patterns. Understanding the intricate role of ADAR1-mediated A>I(G) RNA editing in breast cancer holds significant promise for the development of personalized treatment approaches tailored to individual patients’ A>I(G) RNA-editing profiles.</jats:p>
Scopus© Citations 2 2
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Teneurin protein family: An emerging role in human tumorigenesis and drug resistance
(2012)
Annemarie Ziegler
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Alejandro Corvalán
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Iván Roa
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Jorge A. Brañes
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Bernd Wollscheid
Scopus© Citations 33 1
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Atovaquone/Proguanil Resistance in an Imported Malaria Case in Chile
(2021)
Stella M. Chenet
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Alan Oyarce
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Jorge Fernandez
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Rafael Tapia-Limonchi
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WEITZEL, THOMAS
<jats:title>ABSTRACT</jats:title><jats:p>In November 2018, we diagnosed a cluster of falciparum malaria cases in three Chilean travelers returning from Nigeria. Two patients were treated with sequential intravenous artesunate plus oral atovaquone/proguanil (AP) and one with oral AP. The third patient, a 23-year-old man, presented with fever on day 29 after oral AP treatment and was diagnosed with recrudescent falciparum malaria. The patient was then treated with oral mefloquine, followed by clinical recovery and resolution of parasitemia. Analysis of day 0 and follow-up blood samples, collected on days 9, 29, 34, 64, and 83, revealed that parasitemia had initially decreased but then increased on day 29. Sequencing confirmed Tyr268Cys mutation in the <jats:italic>cytochrome b</jats:italic> gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and <jats:italic>P. falciparum dihydrofolate reductase</jats:italic> mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples. Molecular characterization of imported malaria contributes to clinical management in non-endemic countries, helps ascertain the appropriateness of antimalarial treatment policies, and contributes to the reporting of drug resistance patterns from endemic regions.</jats:p>
4Scopus© Citations 5
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Extracellular Vesicles as Mediators of Cancer Disease and as Nanosystems in Theranostic Applications
(2021)
Renato Burgos-Ravanal
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América Campos
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Magda C. Díaz-Vesga
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María Fernanda González
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Daniela León
<jats:p>Cancer remains a leading cause of death worldwide despite decades of intense efforts to understand the molecular underpinnings of the disease. To date, much of the focus in research has been on the cancer cells themselves and how they acquire specific traits during disease development and progression. However, these cells are known to secrete large numbers of extracellular vesicles (EVs), which are now becoming recognized as key players in cancer. EVs contain a large number of different molecules, including but not limited to proteins, mRNAs, and miRNAs, and they are actively secreted by many different cell types. In the last two decades, a considerable body of evidence has become available indicating that EVs play a very active role in cell communication. Cancer cells are heterogeneous, and recent evidence reveals that cancer cell-derived EV cargos can change the behavior of target cells. For instance, more aggressive cancer cells can transfer their “traits” to less aggressive cancer cells and convert them into more malignant tumor cells or, alternatively, eliminate those cells in a process referred to as “cell competition”. This review discusses how EVs participate in the multistep acquisition of specific traits developed by tumor cells, which are referred to as “the hallmarks of cancer” defined by Hanahan and Weinberg. Moreover, as will be discussed, EVs play an important role in drug resistance, and these more recent advances may explain, at least in part, why pharmacological therapies are often ineffective. Finally, we discuss literature proposing the use of EVs for therapeutic and prognostic purposes in cancer.</jats:p>
1Scopus© Citations 24
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Socioeconomic factors associated with antimicrobial resistance of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli in Chilean hospitals (2008–2017)
(2020)
Kasim Allel
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Patricia García
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Jaime Labarca
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MUNITA SEPULVEDA, JOSE MANUEL
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Magdalena Rendic
To identify socioeconomic factors associated with antimicrobial resistance of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli in Chilean hospitals (2008–2017). <bold>Methods.</bold> We reviewed the scientific literature on socioeconomic factors associated with the emergence and dissemination of antimicrobial resistance. Using multivariate regression, we tested findings from the literature drawing from a longitudinal dataset on antimicrobial resistance from 41 major private and public hospitals and a nationally representative household survey in Chile (2008–2017). We estimated resistance rates for three priority antibiotic–bacterium pairs, as defined by the Organisation for Economic Co-operation and Development; i.e., imipenem and meropenem resistant P. aeruginosa, cloxacillin resistant S. aureus, and cefotaxime and ciprofloxacin resistant E. coli. <bold>Results.</bold> Evidence from the literature review suggests poverty and material deprivation are important risk factors for the emergence and transmission of antimicrobial resistance. Most studies found that worse socioeconomic indicators were associated with higher rates of antimicrobial resistance. Our analysis showed an overall antimicrobial resistance rate of 32.5%, with the highest rates for S. aureus (40.6%) and the lowest for E. coli (25.7%). We found a small but consistent negative association between socioeconomic factors (income, education, and occupation) and overall antimicrobial resistance in univariate (p < 0.01) and multivariate analyses (p < 0.01), driven by resistant P. aeruginosa and S. aureus. <bold>Conclusion.</bold> Socioeconomic factors beyond health care and hospital settings may affect the emergence and dissemination of antimicrobial resistance. Preventing and controlling antimicrobial resistance requires efforts above and beyond reducing antibiotic consumption.
3Scopus© Citations 29
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Resistencia a antibióticos de última línea en cocos Gram positivos: la era posterior a la vancomicina
(2014)
Sandra Rincón
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Diana Panesso
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Lorena Díaz
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Lina P. Carvajal
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Jinnethe Reyes
Scopus© Citations 30 1
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Modified natural cycle IVF versus conventional stimulation in advanced-age Bologna poor responders
(2019)
Panagiotis Drakopoulos
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Alessia Romito
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ERRAZURIZ VALENZUELA, JOAQUIN GABRIEL
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Samuel Santos-Ribeiro
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Biljana Popovic-Todorovic
Scopus© Citations 17 2

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