scholarly journals Phage Resistance Mechanisms Increase Colistin Sensitivity in Acinetobacter baumannii

2021 ◽  
Author(s):  
Xiaoqing Wang ◽  
Belinda Loh ◽  
Yunsong Yu ◽  
Xiaoting Hua ◽  
Sebastian Leptihn

Few emergency-use antibiotics remain for the treatment of multidrug-resistant bacterial infections. Infections with resistant bacteria are becoming increasingly common. Phage therapy has reemerged as a promising strategy to treat such infections, as microbial viruses are not affected by bacterial resistance to antimicrobial compounds. However, phage therapy is impeded by rapid emergence of phage-resistant bacteria during therapy. In this work, we studied phage-resistance of colistin sensitive and resistant A. baumannii strains. Using whole genome sequencing, we determined that phage resistant strains displayed mutations in genes that alter the architecture of the bacterial envelope. In contrast to previous studies where phage-escape mutants showed decreased binding of phages to the bacterial envelope, we obtained several not uninfectable isolates that allowed similar phage adsorption compared to the susceptible strain. When phage-resistant bacteria emerged in the absence of antibiotics, we observed that the colistin resistance levels often decreased, while the antibiotic resistance mechanism per se remained unaltered. In particular the two mutated genes that conveyed phage resistance, a putative amylovoran- biosynthesis and a lipo-oligosaccharide (LOS) biosynthesis gene, impact colistin resistance as the mutations increased sensitivity to the antibiotic.

2006 ◽  
Vol 7 (4) ◽  
pp. 211-222
Author(s):  
Mario Venditti ◽  
Maria Elena Pompeo ◽  
Flavia Fabi

Tigecycline is a new first-in-class glycylcycline antimicrobial agent with expanded broad-spectrum activity. It was developed to overcome the two key resistance mechanisms, efflux pumps and ribosomal protection, that limit the use of tetracycline. The spectrum of activity extends to clinically relevant susceptible and multidrug resistant bacteria, as methicillin resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, vancomycin resistant Enterococci, Acinetobacter spp, Acinetobacter baumannii and Enterobacteriaceae, including extended-spectrum β-lactamase-producing strains (ESBLs). Tigecycline has been introduced into clinical practice as part of the effort to combat the growing problem of bacterial resistance to anti-infective therapy: tigecycline could replace some broad-spectrum agents for approved indications reducing the selective pressure provided by antibiotic administration. The expanded in vitro activity against a broad range of bacteria, including resistant pathogens, of tigecycline suggest that this novel antimicrobial agent should offer clinicians an option for the treatment of patients with serious bacterial infections.


2017 ◽  
Vol 63 (11) ◽  
pp. 865-879 ◽  
Author(s):  
Ayman El-Shibiny ◽  
Salma El-Sahhar

Since their discovery in 1915, bacteriophages have been used to treat bacterial infections in animals and humans because of their unique ability to infect their specific bacterial hosts without affecting other bacterial populations. The research carried out in this field throughout the 20th century, largely in Georgia, part of USSR and Poland, led to the establishment of phage therapy protocols. However, the discovery of penicillin and sulfonamide antibiotics in the Western World during the 1930s was a setback in the advancement of phage therapy. The misuse of antibiotics has reduced their efficacy in controlling pathogens and has led to an increase in the number of antibiotic-resistant bacteria. As an alternative to antibiotics, bacteriophages have become a topic of interest with the emergence of multidrug-resistant bacteria, which are a threat to public health. Recent studies have indicated that bacteriophages can be used indirectly to detect pathogenic bacteria or directly as biocontrol agents. Moreover, they can be used to develop new molecules for clinical applications, vaccine production, drug design, and in the nanomedicine field via phage display.


2020 ◽  
Vol 117 (37) ◽  
pp. 22967-22973
Author(s):  
Amanda C. Zangirolami ◽  
Lucas D. Dias ◽  
Kate C. Blanco ◽  
Carolina S. Vinagreiro ◽  
Natalia M. Inada ◽  
...  

Hospital-acquired infections are a global health problem that threatens patients’ treatment in intensive care units, causing thousands of deaths and a considerable increase in hospitalization costs. The endotracheal tube (ETT) is a medical device placed in the patient’s trachea to assist breathing and delivering oxygen into the lungs. However, bacterial biofilms forming at the surface of the ETT and the development of multidrug-resistant bacteria are considered the primary causes of ventilator-associated pneumonia (VAP), a severe hospital-acquired infection for significant mortality. Under these circumstances, there has been a need to administrate antibiotics together. Although necessary, it has led to a rapid increase in bacterial resistance to antibiotics. Therefore, it becomes necessary to develop alternatives to prevent and combat these bacterial infections. One possibility is to turn the ETT itself into a bactericide. Some examples reported in the literature present drawbacks. To overcome those issues, we have designed a photosensitizer-containing ETT to be used in photodynamic inactivation (PDI) to avoid bacteria biofilm formation and prevent VAP occurrence during tracheal intubation. This work describes ETT’s functionalization with curcumin photosensitizer, as well as its evaluation in PDI against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. A significant photoinactivation (up to 95%) against Gram-negative and Gram-positive bacteria was observed when curcumin-functionalized endotracheal (ETT-curc) was used. These remarkable results demonstrate this strategy’s potential to combat hospital-acquired infections and contribute to fighting antimicrobial resistance.


2007 ◽  
Vol 79 (12) ◽  
pp. 2143-2153 ◽  
Author(s):  
John B. Bremner

Bacteria use a number of resistance mechanisms to counter the antibacterial challenge, and one of these is the expression of transmembrane protein-based efflux pumps which can pump out antibacterials from within the cells, thus lowering the antibacterial concentration to nonlethal levels. For example, in S. aureus, the NorA pump can pump out the antibacterial alkaloid berberine and ciprofloxacin. One general strategy to reduce the health threat of resistant bacteria is to block a major bacterial resistance mechanism at the same time as interfering with another bacterial pathway or target site. New developments of this approach in the context of dual-action prodrugs and dual-action (or hybrid) drugs in which one action is targeted at blocking the NorA efflux pump and the second action at an alternative bacterial target site (or sites) for the antibacterial action are discussed. The compounds are based on a combination of 2-aryl-5-nitro-1H-indole derivatives (as the NorA efflux pump blocking component) and derivatives of berberine. General design principles, syntheses, antibacterial testing, and preliminary work on modes of action studies are discussed.


Author(s):  
Johanna M. Vanegas ◽  
Lorena Salazar-Ospina ◽  
Gustavo A. Roncancio ◽  
Julián Builes ◽  
Judy Natalia Jiménez

ABSTRACT The emergence of resistance mechanisms not only limits the therapeutic options for common bacterial infections but also worsens the prognosis in patients who have conditions that increase the risk of bacterial infections. Thus, the effectiveness of important medical advances that seek to improve the quality of life of patients with chronic diseases is threatened. We report the simultaneous colonization and bacteremia by multidrug-resistant bacteria in two hemodialysis patients. The first patient was colonized by carbapenem- and colistin-resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA). The patient had a bacteremia by MRSA, and molecular typing methods confirmed the colonizing isolate was the same strain that caused infection. The second case is of a patient colonized by extended-spectrum beta-lactamases (ESBL)-producing Escherichia coli and carbapenem-resistant Pseudomonas aeruginosa. During the follow-up period, the patient presented three episodes of bacteremia, one of these caused by ESBL-producing E. coli. Molecular methods confirmed colonization by the same clone of ESBL-producing E. coli at two time points, but with a different genetic pattern to the strain isolated from the blood culture. Colonization by multidrug-resistant bacteria allows not only the spread of these microorganisms, but also increases the subsequent risk of infections with limited treatments options. In addition to infection control measures, it is important to establish policies for the prudent use of antibiotics in dialysis units.


Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 151
Author(s):  
Tatjana Kirtikliene ◽  
Aistė Mierauskaitė ◽  
Ilona Razmienė ◽  
Nomeda Kuisiene

Bacterial resistance to antimicrobial agents plays an important role in the treatment of bacterial infections in healthcare institutions. The spread of multidrug-resistant bacteria can occur during inter- and intra-hospital transmissions among patients and hospital personnel. For this reason, more studies must be conducted to understand how resistance occurs in bacteria and how it moves between hospitals by comparing data from different years and looking out for any patterns that might emerge. Multidrug-resistant (MDR) Acinetobacter spp. was studied at 14 healthcare institutions in Lithuania during 2014, 2016, and 2018 using samples from human bloodstream infections. In total, 194 isolates were collected and identified using MALDI-TOF and VITEK2 analyzers as Acinetobacter baumannii group bacteria. After that, the isolates were analyzed for the presence of different resistance genes (20 genes were analyzed) and characterized by using the Rep-PCR and MLVA (multiple-locus variable-number tandem repeat analysis) genotyping methods. The results of the study showed the relatedness of the different Acinetobacter spp. isolates and a possible circulation of resistance genes or profiles during the different years of the study. This study provides essential information, such as variability and diversity of resistance genes, genetic profiling, and clustering of isolates, to better understand the antimicrobial resistance patterns of Acinetobacter spp. These results can be used to strengthen the control of multidrug-resistant infections in healthcare institutions and to prevent potential outbreaks of this pathogen in the future.


Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 145
Author(s):  
Andrew Vaitekenas ◽  
Anna S. Tai ◽  
Joshua P. Ramsay ◽  
Stephen M. Stick ◽  
Anthony Kicic

Antimicrobial resistance poses a significant threat to modern healthcare as it limits treatment options for bacterial infections, particularly impacting those with chronic conditions such as cystic fibrosis (CF). Viscous mucus accumulation in the lungs of individuals genetically predisposed to CF leads to recurrent bacterial infections, necessitating prolonged antimicrobial chemotherapy. Pseudomonas aeruginosa infections are the predominant driver of CF lung disease, and airway isolates are frequently resistant to multiple antimicrobials. Bacteriophages, or phages, are viruses that specifically infect bacteria and are a promising alternative to antimicrobials for CF P. aeruginosa infections. However, the narrow host range of P. aeruginosa-targeting phages and the rapid evolution of phage resistance could limit the clinical efficacy of phage therapy. A promising approach to overcome these issues is the strategic development of mixtures of phages (cocktails). The aim is to combine phages with broad host ranges and target multiple distinct bacterial receptors to prevent the evolution of phage resistance. However, further research is required to identify and characterize phage resistance mechanisms in CF-derived P. aeruginosa, which differ from their non-CF counterparts. In this review, we consider the mechanisms of P. aeruginosa phage resistance and how these could be overcome by an effective future phage therapy formulation.


2016 ◽  
Vol 29 (2) ◽  
pp. 450-457 ◽  
Author(s):  
CARLA SILVA DA SILVEIRA ◽  
OSCARINA VIANA DE SOUSA ◽  
NORMA SUELY EVANGELISTA-BARRETO

ABSTRACT: In recent years, the emergence of resistant pathogens has complicated the treatment of bacterial infections in livestock production as well as in the medical field, due to the development of resistance mechanisms by microorganisms. The objective of this study was to delineate the antimicrobial resistance profile of Salmonella spp. strains isolated from bivalve mollusks (oysters and mussels) and from estuarine environment water of two regions of Bahia, Brazil. Twenty-seven strains, 12 isolated from bivalve mollusks and 15 from estuarine water, were tested. Eight antimicrobial agents (phenicol, beta-lactams, tetracyclines, quinolones and fluoroquinolones classes) were used for a susceptibility test, Minimum Inhibitory Concentration (MIC) and extended-spectrum beta-lactamases (ESBLs) production. Isolates showed high susceptibility to the classes of antimicrobial agents tested, with resistance only to nalidixic acid (27%), ampicillin (25%) and tetracycline (25%). Bacterial resistance was of chromosomal origin and the multidrug resistance index (MAR) among isolates of shellfish (mussels in natura) was 0.25. The MIC was found to be 100 µg/mL, 500 µg/mL and 350 µg/mL to nalidixic acid, ampicillin and tetracycline, respectively. None of the isolates presented ESBLs production. The presence of multidrug-resistant and high MIC Salmonella spp. is being conveyed in extraction areas of bivalve mollusks in the State of Bahia, Brazil.


Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 739
Author(s):  
Jean-Philippe Lavigne ◽  
Jérémy Ranfaing ◽  
Catherine Dunyach-Rémy ◽  
Albert Sotto

Urinary tract infections (UTIs) are the most common bacterial infections around the world. Uropathogenic Escherichia coli (UPEC) is among the main pathogens isolated in UTIs. The rate of UPEC with high resistance towards antibiotics and multidrug-resistant bacteria have increased dramatically and conduct to the difficulty to treat UTIs. Due to the rarefaction of new antibiotics molecules, new alternative strategies must be evaluated. Since many years, propolis has demonstrated an interesting antibacterial activity against E. coli. Here, we evaluated its activity added to antibiotics on a panel of UPEC with different resistance mechanisms. Minimal inhibitory concentrations (MICs) and time–kill curves of fosfomycin, ceftriaxone, ertapenem and ofloxacin, with and without propolis, were determined. Significant diminution of the MICs was observed using ceftriaxone or ofloxacin + propolis. Propolis alone had a bacteriostatic activity with time-dependent effect against UPEC. The addition of this nutraceutical improved the effect of all the antibiotics evaluated (except fosfomycin) and showed a synergistic bactericidal effect (fractional inhibitory concentrations index ≤ 0.5 and a decrease ≥ 2 log CFU/mL for the combination of propolis plus antibiotics compared with the antibiotic alone). Propolis is able to restore in vitro antibiotic susceptibility when added to antibiotics against UPEC. This study showed that propolis could enhance the efficiency of antibiotics used in UTIs and could represent an alternative solution.


2019 ◽  
Vol 20 (11) ◽  
pp. 2808 ◽  
Author(s):  
Nereyda Niño-Martínez ◽  
Marco Felipe Salas Orozco ◽  
Gabriel-Alejandro Martínez-Castañón ◽  
Fernando Torres Méndez ◽  
Facundo Ruiz

The increase in bacterial resistance to one or several antibiotics has become a global health problem. Recently, nanomaterials have become a tool against multidrug-resistant bacteria. The metal and metal oxide nanoparticles are one of the most studied nanomaterials against multidrug-resistant bacteria. Several in vitro studies report that metal nanoparticles have antimicrobial properties against a broad spectrum of bacterial species. However, until recently, the bacterial resistance mechanisms to the bactericidal action of the nanoparticles had not been investigated. Some of the recently reported resistance mechanisms include electrostatic repulsion, ion efflux pumps, expression of extracellular matrices, and the adaptation of biofilms and mutations. The objective of this review is to summarize the recent findings regarding the mechanisms used by bacteria to counteract the antimicrobial effects of nanoparticles.


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