Article
Medicine, General & Internal
Fernando L. Gordillo Altamirano, Xenia Kostoulias, Dinesh Subedi, Denis Korneev, Anton Y. Peleg, Jeremy J. Barr
Summary: This study demonstrates that the combination of phage and ceftazidime has a significant bactericidal effect against Acinetobacter baumannii AB900 in vivo. The combination treatment group showed a lower bacterial burden compared to the other treatment groups, suggesting that the combination therapy may be an effective strategy for treating multidrug-resistant Acinetobacter baumannii infections.
Review
Biochemistry & Molecular Biology
Danaboina Srikanth, Swanand Vinayak Joshi, Mahammad Ghouse Shaik, Gaurav Pawar, Sushmitha Bujji, Vinaykumar Kanchupalli, Sidharth Chopra, Srinivas Nanduri
Summary: This review provides an overview of the mechanisms and importance of Acinetobacter baumannii resistance as a critical WHO priority pathogen. It also discusses different classes of inhibitors and adjuvants that enhance the effect of existing antibiotics.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Takehiro Nishimura, Teppei Kawahara, Noritaka Kagaya, Yusuke Ogura, Hirosato Takikawa, Hikaru Suenaga, Masaatsu Adachi, Takatsugu Hirokawa, Takayuki Doi, Kazuo Shin-Ya
Summary: JBIR-155 was discovered as a novel specific class D beta-lactamase inhibitor from Streptomyces polymachus SoB100815Hv02. It showed inhibitory activity against the class D beta-lactamase with an IC50 value of 0.36 μM. The compound consists of a 6-oxabicyclo[3.2.0]heptan-7-one skeleton and a long unsaturated alkyl chain moiety.
Article
Infectious Diseases
Alyona Lavrinenko, Eugene Sheck, Svetlana Kolesnichenko, Ilya Azizov, Anar Turmukhambetova
Summary: The study aimed to determine the prevalence of A. baumannii antibiotic-resistant strains in Kazakhstan and identified high-risk clones associated with carbapenem resistance. The majority of resistant strains belonged to the CG208(92)(OXF)/CG2(PAS) clonal group, indicating a significant spread of carbapenem resistance in the region.
Article
Microbiology
Piyatip Khuntayaporn, Pohnvipa Kanathum, Jantana Houngsaitong, Preecha Montakantikul, Krit Thirapanmethee, Mullika Traidej Chomnawang
Summary: This study investigated antimicrobial resistance genes distribution in Acinetobacter baumannii population in Thailand. The predominant sequence type in Thailand was ST2 belonging to IC2, followed by ST164, ST129, and other types. The study revealed the prevalence of blaOXA-23 gene and the effectiveness of colistin against MDR A. baumannii.
ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS
(2021)
Article
Microbiology
Wern Chern Chai, Jonathan J. Whittall, Steven W. Polyak, Klyie Foo, Xin Li, Cameron J. Dutschke, Abiodun D. Ogunniyi, Shutao Ma, Matthew J. Sykes, Susan J. Semple, Henrietta Venter
Summary: Acinetobacter baumannii is a highly drug-resistant pathogen and treatment options for infections caused by this pathogen are limited. This study discovered that cinnamaldehyde analogs have potent antimicrobial activity against A. baumannii and can inhibit its cell division. The safety of these compounds was also assessed through in vitro and in vivo experiments.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Infectious Diseases
Nouf Al-Rashed, Khalid M. Bindayna, Mohammad Shahid, Nermin Kamal Saeed, Abdullah Darwish, Ronni Mol Joji, Ali Al-Mahmeed
Summary: This study collected 50 carbapenem-resistant Acinetobacter baumannii (CRAB) isolates from four main hospitals in Bahrain. The results showed that all isolates were resistant to imipenem, meropenem, and cephalosporins, and harbored various resistance genes. The study emphasizes the importance of strengthening surveillance and stringent infection control measures in clinical settings to prevent the further spread of such isolates.
Article
Immunology
Dimitra Petropoulou, Maria Siopi, Sophia Vourli, Spyros Pournaras
Summary: This study evaluated the in vitro activity of the sulbactam-durlobactam (SD) combination against carbapenem-resistant A. baumannii isolates. SD demonstrated the lowest minimum inhibitory concentration (MIC90) and showed potential utility for the treatment of infections caused by A. baumannii. The addition of imipenem further enhanced the activity of SD.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Greater Kayode Oyejobi, Sunday Olabode Olaniyan, Nana-Aishat Yusuf, Deborah Adepeju Ojewande, Mobolaji Johnson Awopetu, Goodness Opeyemi Oyeniran, Fazal Mehmood Khan, Peter Alabi Dare, Maryam Kikelomo Adegbite-Badmus
Summary: Acinetobacter baumannii is an important nosocomial and opportunistic pathogen with high antibiotic resistance. New treatment approaches like the use of bacteriophage, phage-antibiotic combinations, and resistance-driven fitness losses are crucial for controlling its infections.
MICROBIOLOGICAL RESEARCH
(2022)
Article
Infectious Diseases
Hui Zhang, Peiyao Jia, Ying Zhu, Ge Zhang, Jingjia Zhang, Wei Kang, Simeng Duan, Weijuan Zhang, Qiwen Yang, Yingchun Xu
Summary: This study investigated the susceptibility of imipenem/relebactam for infections caused by A. baumannii and P. aeruginosa in China, showing that the drug is effective in treating MDR or imipenem-non-susceptible P. aeruginosa infections but not A. baumannii infections.
INFECTION AND DRUG RESISTANCE
(2021)
Article
Infectious Diseases
Jacqueline Findlay, Laurent Poirel, Maxime Bouvier, Patrice Nordmann
Summary: This study investigated the resistance mechanisms of carbapenemase-producing Acinetobacter baumannii and evaluated the in vitro antibacterial activity of sulbactam combined with durlobactam. The results showed that sulbactam-durlobactam had excellent activity against A. baumannii isolates and identified potential mechanisms involved in resistance, including PBP substitutions and specific beta-lactamase production.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2022)
Article
Chemistry, Multidisciplinary
Sajal Kumar Halder, Maria Mulla Mim, Md Meharab Hassan Alif, Jannatul Fardous Shathi, Nuhu Alam, Aparna Shil, Mahbubul Kabir Himel
Summary: Antimicrobial resistance is a major global health crisis. Acinetobacter baumannii has been a focus of attention due to its ability to develop multidrug resistance. Researchers have identified the most damaging mutations in A. baumannii using computational tools and molecular dynamics simulations. These findings are important for researchers looking to combat these harmful variants and develop new therapeutics.
Review
Infectious Diseases
Neetu Gupta, Kalpana Angadi, Savita Jadhav
Summary: This review aims to understand the mechanisms of carbapenem resistance, categorize and discuss carbapenemases encoding genes and various mobile genetic elements, as well as the prevalence of carbapenemase genes in recent years in A. baumannii from various geographical regions.
INFECTION AND DRUG RESISTANCE
(2022)
Article
Infectious Diseases
Nayeong Kim, Joo-Hee Son, Kyeongmin Kim, Hyo-Jeong Kim, Minsang Shin, Je-Chul Lee
Summary: The study found that DksA plays a regulatory role in the antimicrobial susceptibility of Acinetobacter baumannii, with increment dksA mutant strains showing increased susceptibility to quinolones and tetracyclines but decreased susceptibility to aminoglycosides, and upregulation of efflux pump gene expression. In contrast, (p)ppGpp-deficient mutants downregulate efflux pump gene expression, indicating that (p)ppGpp and DksA have opposite roles in modulating antimicrobial susceptibility via efflux pump gene regulation in A. baumannii.
Article
Microbiology
Lamiaa A. Al-Madboly
Summary: The study found that combining sodium ascorbate and apo-transferrin with imipenem can effectively enhance the antimicrobial effect against carbapenem-resistant A. baumannii, achieving synergy and significantly reducing the minimum inhibitory concentration of imipenem. In vitro experiments also demonstrated a strong bactericidal effect of the triple combination, with almost zero bacterial count at 10 hours.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Alba Ruedas-Lopez, Isaac Alonso-Garcia, Cristina Lasarte-Monterrubio, Paula Guijarro-Sanchez, Eva Gato, Juan Carlos Vazquez-Ucha, Juan Andres Vallejo, Pablo Arturo Fraile-Ribot, Begona Fernandez-Perez, David Velasco, Jose Maria Gutierrez-Urbon, Marina Oviano, Alejandro Beceiro, Concepcion Gonzalez-Bello, Antonio Oliver, Jorge Arca-Suarez, German Bou
Summary: This study aimed to analyze the resistance mechanisms of ceftolozane-tazobactam and ceftazidime-avibactam in multidrug-resistant or extensively drug-resistant P. aeruginosa isolates. The findings revealed that most of the resistant isolates were recovered after treatment with ceftolozane-tazobactam or ceftazidime-avibactam. Chromosomal mutations and specific gene substitutions were identified as the main resistance mechanisms. The study emphasized the potential selection of MDR/XDR P. aeruginosa strains producing certain variants or metallo-beta-lactamases by cephalosporin/beta-lactamase inhibitors, and encouraged judicious use of these agents.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Water Resources
Sandra Raposo-Garcia, David Castro, Emilio Lence, Pablo Estevez, Jose Manuel Leao, Concepcion Gonzalez-Bello, Ana Gago-Martinez, M. Carmen Louzao, Carmen Vale, Luis M. Botana
Summary: This study presents an integrated approach to compare the cytotoxicity and binding mode of Caribbean and Pacific ciguatoxins in sodium channels. The results demonstrate similar cytotoxicity and asymmetric binding of the toxins, providing insights into their biological effects.
EXPOSURE AND HEALTH
(2023)
Article
Biotechnology & Applied Microbiology
Pablo Aja-Macaya, Soraya Rumbo-Feal, Margarita Poza, Angelina Canizares, Juan A. A. Vallejo, German Bou
Summary: A new method for extraction and enrichment of genomic MPXV DNA was developed, which significantly improved the sequencing efficiency and trustworthiness of the consensus sequences. Enriched samples contained a higher percentage of MPXV reads compared to non-enriched samples, leading to more accurate and cost-effective diagnosis of contagious diseases.
Article
Biochemistry & Molecular Biology
Guillermo Garcia-Lainez, Meryem El Ouardi, Alejandro Moreno, Emilio Lence, Concepcion Gonzalez-Bello, Miguel A. Miranda, Inmaculada Andreu
Summary: Hepatitis C, caused by hepatitis C virus, is treated with antiviral drugs. Simeprevir (SIM), an NS3/4A protease inhibitor, is effective in genotypes 1 and 4. However, SIM treatment can lead to photosensitivity reactions, and in vitro experiments show that SIM has phototoxic effects on cells and can cause damage to cellular membranes, lipids, and DNA.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Infectious Diseases
Juan Carlos Vazquez-Ucha, Isaac Alonso-Garcia, Paula Guijarro-Sanchez, Cristina Lasarte-Monterrubio, Laura Alvarez-Fraga, Arnau Cendon-Esteve, Michelle Outeda, Romina Maceiras, Andrea Pena-Escolano, Marta Martinez-Guitian, Jorge Arca-Suarez, German Bou, Alejandro Beceiro
Summary: Metallo- ,B-lactamase (MBL)-producing Enterobacterales, which are resistant to almost all ,B-lactam antibiotics, pose a significant threat due to their wide dissemination and difficulty in treatment. This study evaluated the activity of aztreonam in combination with novel ,B-lactamase inhibitors (BLIs) against clinical isolates co-producing MBLs and SBLs. The results showed that aztreonam/zidebactam, aztreonam/avibactam, and aztreonam/taniborbactam were the most effective combinations, offering promising therapeutic strategies for difficult-to-treat infections.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Biochemistry & Molecular Biology
Angela Rodriguez, Maria Maneiro, Emilio Lence, Jose M. Otero, Mark J. J. van Raaij, Paul Thompson, Alastair R. R. Hawkins, Concepcion Gonzalez-Bello
Summary: This study explores irreversible inhibition of DHQ1 enzyme by enhancing the electrophilicity of ligand and utilizing the acid-base properties of amino substituents. Compound 6, with a hydroxyamino substituent, serves as a time-dependent irreversible inhibitor, while compounds 7 and 8 do not allow enzyme modification. Crystal structures analysis and molecular dynamics simulation provide insights into the molecular basis of this inhibition. This research emphasizes the importance of achieving the correct geometry between the ligand and enzyme for selective covalent modification.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Microbiology
Cristina Lasarte-Monterrubio, Paula Guijarro-Sanchez, Juan Carlos Vazquez-Ucha, Isaac Alonso-Garcia, Laura Alvarez-Fraga, Michelle Outeda, Marta Martinez-Guitian, Andrea Pena-Escolano, Romina Maceiras, Emilio Lence, Concepcion Gonzalez-Bello, Jorge Arca-Suarez, German Bou, Alejandro Beceiro
Summary: Resistance to cefiderocol has emerged among carbapenemase-producing Enterobacterales, particularly in the Enterobacter cloacae complex. This resistance is mainly due to the production of VIM-1 carbapenemase and may also involve the co-production of SHV-12 and inactivation of the FcuA-like siderophore receptor.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Chemistry, Medicinal
Diana Rodriguez, Concepcion Gonzalez-Bello
Summary: The success of precision medicine and the negative impact of broad-spectrum antibiotics on microbiome stability and bacterial resistance have led to a shift towards precision antibiotics. A novel vectorization approach involves conjugating antibiotics to siderophores, which facilitate internalization into deadly gram-negative pathogens through bacterial iron uptake pathways. This approach has shown promising results, as demonstrated by the commercialization of cefiderocol, the first antibiotic based on this principle. This review provides an overview of the molecular basis, successful examples, and future challenges of antibiotic-siderophore conjugation.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Infectious Diseases
Isaac Alonso-Garcia, Juan Carlos Vazquez-Ucha, Cristina Lasarte-Monterrubio, Elena Gonzalez-Mayo, Paula Lada-Salvador, Ramon Vela-Fernandez, Pablo Aja-Macaya, Paula Guijarro-Sanchez, Soraya Rumbo-Feal, Maria Muino-Andrade, Ana Fernandez-Gonzalez, Marta Martinez-Guitian, Alejandro Beceiro, Manuel Rodriguez-Iglesias, Antonio Oliver, Jorge Arca-Suarez, Fatima Galan-Sanchez, German Bou
Summary: This study described and characterized the emergence of resistance to ceftolozane/tazobactam, ceftazidime/avibactam, and imipenem/relebactam in a patient with MDR Pseudomonas aeruginosa central nervous system infection. Mutational changes in the bacteria's genes were investigated through whole genome sequencing, and it was found that mutations in the P PDC beta-lactamase and MexAB-OprM regulator MexR played a role in the development of resistance. Cloning experiments and complementation assays confirmed the impact of the mutations on resistance. The study highlights the ability of P. aeruginosa to develop resistance and compromise the activity of new beta-lactam/beta-lactamase inhibitor combinations.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Isaac Alonso-Garcia, Juan Carlos Vazquez-Ucha, Marta Martinez-Guitian, Cristina Lasarte-Monterrubio, Salud Rodriguez-Pallares, Pablo Camacho-Zamora, Soraya Rumbo-Feal, Pablo Aja-Macaya, Lucia Gonzalez-Pinto, Michelle Outeda-Garcia, Romina Maceiras, Paula Guijarro-Sanchez, Maria Jose Muino-Andrade, Ana Fernandez-Gonzalez, Marina Oviano, Concepcion Gonzalez-Bello, Jorge Arca-Suarez, Alejandro Beceiro, German Bou
Summary: The impact of the β-lactamase OXA-10 on carbapenem resistance in Enterobacterales was investigated through various experiments. The results demonstrated that OXA-10 contributes to increased carbapenem minimum inhibitory concentrations when combined with porin deficiency. However, OXA-10 was not detected using standard biochemical tests.
Article
Infectious Diseases
Eva Gato, Paula Guijarro-Sanchez, Isaac Alonso-Garcia, Rosa Pedraza-Merino, Adrian Conde, Emilio Lence, Soraya Rumbo-Feal, Andrea Pena-Escolano, Cristina Lasarte-Monterrubio, Tania Blanco-Martin, Ana Fernandez-Gonzalez, M. del Carmen Fernandez-Lopez, Romina Maceiras, Marta Martinez-Guitian, Juan Carlos Vazquez-Ucha, Luis Martinez-Martinez, Concepcion Gonzalez-Bello, Jorge Arca-Suarez, Alejandro Beceiro, German Bou
Summary: By studying high-risk Klebsiella pneumoniae strains, we found that imipenem/relebactam was more effective than ceftazidime/avibactam in preventing resistance mutations. In some strains, imipenem/relebactam resistance developed faster and reached higher levels compared to ceftazidime/avibactam. Lineages that evolved in the presence of ceftazidime/avibactam showed KPC substitutions associated with high-level resistance, while lineages that evolved in the presence of imipenem/relebactam showed specific substitutions related to imipenem/relebactam resistance.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)