Review
Microbiology
George Tetz, Victor Tetz
Summary: Conventional antimicrobial susceptibility tests fail to accurately identify effective antibiotics due to their neglect of the impact of multispecies bacterial communities and simultaneous infections by multiple pathogens. This review comprehensively outlines the factors missed by conventional tests and explains how considering these factors can aid the development of novel diagnostic approaches.
Review
Microbiology
Ascension Rueda-Robles, Avilene Rodriguez-Lara, Matthew S. Meyers, Maria Jose Saez-Lara, Ana Alvarez-Mercado
Summary: Diseases caused by bacteria and antibiotic resistance are important global issues. Persistence of bacteria is a survival strategy, and probiotics can regulate gut microbiota, inhibit pathogen growth, and replace pathogenic bacteria.
Article
Multidisciplinary Sciences
Markus Huemer, Srikanth Mairpady Shambat, Judith Bergada-Pijuan, Sandra Soderholm, Mathilde Boumasmoud, Clement Vulin, Alejandro Gomez-Mejia, Minia Antelo Varela, Vishwachi Tripathi, Sandra Gotschi, Ewerton Marques Maggio, Barbara Hasse, Silvio D. Brugger, Dirk Bumann, Reto A. Schuepbach, Annelies S. Zinkernagel
Summary: Staphylococcus aureus persisters, formed under host-mediated stress, display unique growth characteristics and molecular reprogramming, requiring specific metabolic pathways for maintenance. These non-metabolically active persisters regain virulence potential upon regrowth, exhibiting a reversible state crucial for recurrent infections. Targeted antipersister combination therapy significantly reduces lag-phase heterogeneity and persisters, providing insights into the difficulty of treating persistent S. aureus infections.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Immunology
Sarah E. Rowe, Jenna E. Beam, Brian P. Conlon
Summary: Antibiotic treatment failure of Staphylococcus aureus infections is common, with various factors limiting antibiotic efficacy in vivo; one major obstacle is the ability of S. aureus to enter a physiological state incompatible with antibiotic killing. To address the problem of recalcitrant S. aureus infection, specific approaches targeting tolerant cells within different niches may be required, including direct targeting of persister cells or improved penetration of antibiotics to particular niches.
INFECTION AND IMMUNITY
(2021)
Article
Infectious Diseases
Minjeong Kang, Tae-Rim Choi, Soyeon Ahn, Hee Young Heo, Hyerim Kim, Hye Soo Lee, Yoo Kyung Lee, Hwang-Soo Joo, Philip S. Yune, Wooseong Kim, Yung-Hun Yang
Summary: Bacteria can evade antibiotics through acquiring resistance genes and switching to a dormant state. Our study found that the cold-adapted bacterium Pseudomonas sp. B14-6 showed resistance and tolerance to aminoglycosides, and this ability appears to be related to reduced metabolic activity.
Article
Immunology
Federico Perez, Roberto Viau Colindres, Brigid M. Wilson, Elie Saade, Robin L. P. Jump, Ritu Banerjee, Robin Patel, Scott R. Evans, Robert A. Bonomo
Summary: The study used the DOOR MAT approach to evaluate antibiotic treatment of E. coli and K. pneumoniae bloodstream infections in VHA patients across a decade. Over the 10-year period, resistance to certain antibiotics increased in E. coli but remained stable in K. pneumoniae. Discrepancy between empiric and definitive treatment desirability narrowed, with no negative impact on patient survival.
CLINICAL INFECTIOUS DISEASES
(2021)
Review
Infectious Diseases
Alessandra Romandini, Arianna Pani, Paolo Andrea Schenardi, Giulia Angela Carla Pattarino, Costantino De Giacomo, Francesco Scaglione
Summary: Antibiotic resistance poses a significant public health threat to children, with multiple factors contributing to its emergence, including overuse and misuse of antibiotics, lack of pediatric-specific data and trials. The evolving nature of children's development requires consideration of the diversity in biochemical characteristics and pharmacokinetics in drug treatment.
Review
Infectious Diseases
Made Rai Dwitya Wiradiputra, Piyatip Khuntayaporn, Krit Thirapanmethee, Mullika Traidej Chomnawang
Summary: The toxin and antitoxin modules in bacteria are crucial for the formation of persister cells, which can survive antimicrobial treatment without any resistance mechanisms. Salmonella enterica serovar Typhimurium, a prevalent strain, is known to cause persistent infection and the involvement of toxin and antitoxin modules facilitates its survival ability in the presence of antimicrobial agents.
INFECTION AND DRUG RESISTANCE
(2022)
Article
Medicine, General & Internal
Xuhui Li, Hua Fan, Hao Zi, Hankun Hu, Binghui Li, Jiao Huang, Pengcheng Luo, Xiantao Zeng
Summary: This study aimed to estimate the global and regional burden of bacterial antimicrobial resistance (AMR) in urinary tract infections (UTI) in 2019. The results showed that globally, there were approximately 64.89 thousand deaths attributed to and 0.26 million deaths associated with bacterial AMR in UTI. Escherichia coli and Klebsiella pneumoniae had the highest resistance rates, including resistance to fluoroquinolones, carbapenems, and third-generation cephalosporins. Tailored strategies, such as enhanced surveillance and rational use of antibiotics, should be developed for different regions based on their specific pathogen-antibiotic situations and resources.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Immunology
Victoria Palin, William Welfare, Darren M. Ashcroft, Tjeerd Pieter van Staa
Summary: The study found that shorter and longer antibiotic courses have equal effectiveness in reducing infection-related hospitalizations. Therefore, stewardship programs should recommend shorter antibiotic courses for acute infections. No variation by infection-type was observed in this study.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Infectious Diseases
Kibum Jeon, Seri Jeong, Nuri Lee, Min-Jeong Park, Wonkeun Song, Han-Sung Kim, Hyun Soo Kim, Jae-Seok Kim
Summary: The consumption of antibiotics and the prevalence of infections caused by multidrug-resistant (MDR) bacteria have increased during the COVID-19 pandemic.
Review
Infectious Diseases
Keshani Weragama, Poonam Mudgil, John Whitehall
Summary: Antimicrobial resistance is driven by microbial pathogens developing resistance to antibiotics, particularly in pediatric patients presenting with respiratory symptoms in the emergency setting. Antimicrobial stewardship programs have shown effectiveness in reducing antibiotic prescription rates, increasing the use of narrow-spectrum antibiotics, and shortening antibiotic therapy duration, especially when education-based interventions and rapid respiratory pathogen testing are utilized. Further studies are needed to determine if these reductions in antibiotic prescribing translate to improved clinical outcomes.
Article
Infectious Diseases
David Huang, Nicholas Pachuda, John Michael Sauer, Dessie Dobbins, Jonathan Steckbeck
Summary: Antimicrobial peptides (AMPs) are gaining attention as potential treatments for bacterial and viral infections due to the reduced efficacy of traditional antimicrobial drugs. PLG0206, an engineered cationic antibiotic peptide, has selective targeting against bacterial cells, reduces biofilm burdens, and shows broad-spectrum activity against various bacteria. A recent study demonstrated its safety in humans, and further studies are planned to determine its efficacy in patients.
Review
Immunology
Sherry A. Dunbar, Christopher Gardner, Shubhagata Das
Summary: This article describes the application of two rapid, molecular bloodstream infection panels that can identify the most common pathogens and associated genetic determinants of antibiotic resistance, providing clinicians with faster information for treatment. Molecular testing methods reduce the turnaround time for diagnosing bloodstream pathogens to a few hours, helping to initiate timely and effective treatment.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Veterinary Sciences
Lynn M. Pezzanite, Lyndah Chow, Alyssa Strumpf, Valerie Johnson, Steven W. Dow
Summary: Mesenchymal stromal/stem cells possess intrinsic antimicrobial properties and can have enhanced effects through immune activation, making them a potential therapeutic approach for drug-resistant infections. This review explores the use of cellular therapies in veterinary medicine for treating bacterial infections, emphasizing on the antimicrobial activity of MSC and the potential of activated cellular therapy (ACT).
VETERINARY SCIENCES
(2022)
Review
Microbiology
Ana L. Moldoveanu, Julian A. Rycroft, Sophie Helaine
Summary: The rise of antibiotic failure is a significant threat to global health, which is not only driven by stable antibiotic resistance but also by a subpopulation of transiently non-growing, antibiotic tolerant bacteria known as 'persisters'. Recent advances in the field have revealed the complex nature of persisters, highlighting their high adaptability through biosynthetic activity, contributing to the evolution of antimicrobial resistance and modulation of host immune responses despite clinically effective treatment.
CURRENT OPINION IN MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jan Jakub Lica, Milosz Wieczor, Grzegorz Jan Grabe, Mateusz Heldt, Marta Jancz, Majus Misiak, Katarzyna Gucwa, Wioletta Brankiewicz, Natalia Maciejewska, Anna Stupak, Maciej Baginski, Krzysztof Rolka, Andrzej Hellmann, Andrzej Skladanowski
Summary: This study demonstrates the utility of cell density-dependent stage culture profiles in achieving more robust drug activity results, emphasizing the importance of accounting for primitive cell fractions in the assessment of drug efficiency.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Teige R. S. Matthews-Palmer, Nayim Gonzalez-Rodriguez, Thomas Calcraft, Signe Lagercrantz, Tobias Zachs, Xiu-Jun Yu, Grzegorz J. Grabe, David W. Holden, Andrea Nans, Peter B. Rosenthal, Sarah L. Rouse, Morgan Beeby
Summary: Bacterial type III secretion systems play a crucial role in assembling the axial structures of both injectisomes and flagella, while triggering the secretion of effector proteins by sensing the neutral pH of the host cytoplasm. SctV is central to specificity switching, with its structure affecting the binding of the gatekeeper complex in response to pH changes.
JOURNAL OF STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Grzegorz J. Grabe, Rachel T. Giorgio, Alexander M. J. Hall, Rhodri M. L. Morgan, Laurent Dubois, Tyler A. Sisley, Julian A. Rycroft, Stephen A. Hare, Sophie Helaine
Summary: Our research demonstrates that altering a structural element on the toxin drives specific recognition by the cognate antitoxin, leading to insulation of the system. The region supporting TA-specific pairing is crucial for neutralization in the TacAT systems studied. Additionally, other TA interfaces alongside the main neutralization interface increase the safe space for the evolution of pairing specificity.
NATURE CHEMICAL BIOLOGY
(2021)
Review
Microbiology
Severin Ronneau, Peter W. S. Hill, Sophie Helaine
Summary: Antibiotic tolerance and persistence are two phenomena that are superficially similar but have different physiological mechanisms, and need to be distinguished in experimental studies. While antibiotic tolerance arises from genetic mutations or environmental conditions causing growth restriction in bacteria, antibiotic persistence is a challenging transient phenomenon.
CURRENT OPINION IN MICROBIOLOGY
(2021)
Article
Microbiology
Benjamin L. Springstein, Padraig Deighan, Grzegorz J. Grabe, Ann Hochschild
Summary: Understanding the interactions of virally encoded proteins is crucial for unraveling basic viral biology and laying the groundwork for therapeutic advancements. In this study, a convenient bacterial cell-based two-hybrid system was used to analyze the interactions of proteins encoded by SARS-CoV-2, leading to the identification of 16 distinct intraviral protein-protein interactions involving 16 proteins. The system enabled the genetic dissection of these interactions and the detection of selectively disruptive mutations, illustrating the potential for identifying potential therapeutics that disrupt specific interactions of virally encoded proteins, while also demonstrating the general utility of the system for probing viral protein interactions.
Article
Biochemistry & Molecular Biology
Guilherme de Castro, Dennis J. Worm, Grzegorz J. Grabe, Fiona C. Rowan, Lucy Haggerty, Ana L. de la Lastra, Oana Popescu, Sophie Helaine, Anna Barnard
Summary: In this study, a novel method was developed to produce recombinant bacterial toxin Doc, and antitoxin-mimicking peptides were used to investigate the mechanism by which its cognate antitoxin Phd neutralizes the activity of Doc. The study provides insights into the molecular detail of the Phd-Doc relationship and identifies key principles for the development of chemical tools to study and therapeutically interrogate this important class of protein-protein interactions.
ACS CHEMICAL BIOLOGY
(2022)
Article
Microbiology
Yael Yair, Charlotte Michaux, Dvora Biran, Joerg Bernhard, Joerg Vogel, Lars Barquist, Eliora Z. Ron
Summary: The RNA chaperones CspC and CspE play important roles in stress response and adaptation. In this study, we investigated their involvement in the pathogenesis of a virulent strain of Escherichia coli. Using CLIP-seq, we identified numerous transcripts that interact with these cold shock proteins and found that many of these transcripts are involved in protein synthesis, transcription, energy metabolism, and virulence-related processes. Further experiments showed that deleting either CspC or CspE significantly decreased the levels of certain virulence-associated transcripts and resulted in a loss of serum resistance, a key requirement for sepsis. These findings highlight the essential role of these RNA chaperones in the virulence of E. coli.
Article
Microbiology
Stephanie Paulini, Florian D. Fabiani, Anna S. Weiss, Ana Laura Moldoveanu, Sophie Helaine, Baerbel Stecher, Kirsten Jung
Summary: Pyruvate, the simplest of the alpha-keto acids, plays a crucial role in the metabolic pathways of bacteria and eukaryotes. This study identified two specific transporters, BtsT and CstA, in Salmonella enterica serovar Typhimurium, which are important for pyruvate uptake and have significant effects on bacterial survival, infection, and persistence.
Article
Microbiology
Alisa Rizvanovic, Charlotte Michaux, Margherita Panza, Zeynep Iloglu, Sophie Helaine, E. Gerhart H. Wagner, Erik Holmqvist
Summary: Bacteria can avoid antibiotic eradication by forming persister cells through phenotypic heterogeneity. The RNA-binding protein ProQ has been identified as a global regulator of gene expression that promotes persister formation in Salmonella. ProQ activates energy-consuming processes and allows Salmonella to survive in macrophages.
Article
Microbiology
Charlotte Michaux, Severin Ronneae, Rachel T. Giorgio, Sophie Helaine
Summary: Genetically susceptible bacteria can escape the action of antibiotics through antibiotic tolerance or persistence. Tolerance affects the entire bacterial population while persistence only impacts a subset of cells. Tolerance-inducing conditions can mask persistence and impair bacterial proliferation during infection.
Article
Microbiology
Francois Guerin, Francois Gravey, Sophie Reissier, Malo Penven, Charlotte Michaux, Simon Le Hello, Vincent Cattoir
Summary: The Enterobacter cloacae complex (ECC) has become a major opportunistic pathogen with antimicrobial resistance issues. Temocillin, an old carboxypenicillin that is remarkably stable toward beta-lactamases, has been used as an alternative for the treatment of multidrug-resistant ECC infections. By comparative genomic analysis of two clonally related ECC clinical isolates, one susceptible (Temo_S [MIC of 4 mg/L]) and the other resistant (Temo_R [MIC of 32 mg/L]), we found that a single BaeS alteration can lead to temocillin resistance through enhanced active efflux.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Microbiology
Severin Ronneau, Charlotte Michaux, Sophie Helaine
Summary: Internalization of pathogenic bacteria by macrophages results in the formation of antibiotic-tolerant persisters. These cells are maintained in a non-growing state for extended periods of time. After persister formation, host reactive nitrogen species (RNS) produced in response to Salmonella infection lock persisters in growth arrest by intoxicating their TCA cycle. Persister growth resumption within macrophages is slow and heterogeneous, extending the time the persister reservoir feeds infection relapse. The use of an inhibitor of RNS production can force recalcitrant bacteria to regrow during antibiotic treatment, facilitating their eradication.
CELL HOST & MICROBE
(2023)