scholarly journals Bacteriophages: A Revisited Strategy for the Treatment of Severe Bacterial Infections

2020 ◽  
Vol 2 (3) ◽  
pp. 78-79
Author(s):  
Roberto Badaro

Bacteriophages are viruses that infect and parasitize bacteria. The current increase in the incidence of antibiotic resistance in human bacteria has favoredthe study of phages as a therapeutic alternative (phage therapy). Phage therapy is defined as the administration of virulent phages directly to a patient to lyse the bacterial pathogen that is causing a clinically severe infection. The ideal route of administration and modification of bacteriopaghes genetically to deactivate bacterial resistance genes is the next future to antibiotic recovery sensitivity of MDR organisms.

2016 ◽  
Vol 1 (2) ◽  
pp. 22 ◽  
Author(s):  
Navindra Kumari Palanisamy ◽  
Parasakthi Navaratnam ◽  
Shamala Devi Sekaran

Introduction: Streptococcus pneumoniae is an important bacterial pathogen, causing respiratory infection. Penicillin resistance in S. pneumoniae is associated with alterations in the penicillin binding proteins, while resistance to macrolides is conferred either by the modification of the ribosomal target site or efflux mechanism. This study aimed to characterize S. pneumoniae and its antibiotic resistance genes using 2 sets of multiplex PCRs. Methods: A quintuplex and triplex PCR was used to characterize the pbp1A, ermB, gyrA, ply, and the mefE genes. Fifty-eight penicillin sensitive strains (PSSP), 36 penicillin intermediate strains (PISP) and 26 penicillin resistance strains (PRSP) were used. Results: Alteration in pbp1A was only observed in PISP and PRSP strains, while PCR amplification of the ermB or mefE was observed only in strains with reduced susceptibility to erythromycin. The assay was found to be sensitive as simulated blood cultures showed the lowest level of detection to be 10cfu. Conclusions: As predicted, the assay was able to differentiate penicillin susceptible from the non-susceptible strains based on the detection of the pbp1A gene, which correlated with the MIC value of the strains.


2021 ◽  
Vol 22 (13) ◽  
pp. 6891
Author(s):  
João S. Rebelo ◽  
Célia P. F. Domingues ◽  
Francisco Dionisio ◽  
Manuel C. Gomes ◽  
Ana Botelho ◽  
...  

Recently, much attention has been paid to the COVID-19 pandemic. Yet bacterial resistance to antibiotics remains a serious and unresolved public health problem that kills hundreds of thousands of people annually, being an insidious and silent pandemic. To contain the spreading of the SARS-CoV-2 virus, populations confined and tightened hygiene measures. We performed this study with computer simulations and by using mobility data of mobile phones from Google in the region of Lisbon, Portugal, comprising 3.7 million people during two different lockdown periods, scenarios of 40 and 60% mobility reduction. In the simulations, we assumed that the network of physical contact between people is that of a small world and computed the antibiotic resistance in human microbiomes after 180 days in the simulation. Our simulations show that reducing human contacts drives a reduction in the diversity of antibiotic resistance genes in human microbiomes. Kruskal–Wallis and Dunn’s pairwise tests show very strong evidence (p < 0.000, adjusted using the Bonferroni correction) of a difference between the four confinement regimes. The proportion of variability in the ranked dependent variable accounted for by the confinement variable was η2 = 0.148, indicating a large effect of confinement on the diversity of antibiotic resistance. We have shown that confinement and hygienic measures, in addition to reducing the spread of pathogenic bacteria in a human network, also reduce resistance and the need to use antibiotics.


2021 ◽  
Vol 2 ◽  
Author(s):  
Kaixuan Guo ◽  
Yue Zhao ◽  
Luqing Cui ◽  
Zhengzheng Cao ◽  
Fan Zhang ◽  
...  

Bacterial resistance is a complex scientific issue. To manage this issue, we need to deeply understand the influencing factors and mechanisms. Based on the background of livestock husbandry, this paper reviews the factors that affect the acquisition of bacterial resistance. Meanwhile, the resistance mechanism is also discussed. “Survival of the fittest” is the result of genetic plasticity of bacterial pathogens, which brings about specific response, such as producing adaptive mutation, gaining genetic material or changing gene expression. To a large extent, bacterial populations acquire resistance genes directly caused by the selective pressure of antibiotics. However, mobile resistance genes may be co-selected by other existing substances (such as heavy metals and biocides) without direct selection pressure from antibiotics. This is because the same mobile genetic elements as antibiotic resistance genes can be co-located by the resistance determinants of some of these compounds. Furthermore, environmental factors are a source of resistance gene acquisition. Here, we describe some of the key measures that should be taken to mitigate the risk of antibiotic resistance. We call on the relevant governments or organizations around the world to formulate and improve the monitoring policies of antibiotic resistance, strengthen the supervision, strengthen the international cooperation and exchange, and curb the emergence and spread of drug-resistant strains.


mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Susan M. Joseph ◽  
Thomas Battaglia ◽  
Julia M. Maritz ◽  
Jane M. Carlton ◽  
Martin J. Blaser

ABSTRACT Bacterial resistance to antibiotics is a pressing health issue around the world, not only in health care settings but also in the community and environment, particularly in crowded urban populations. The aim of our work was to characterize the microbial populations in sewage and the spread of antibiotic resistance within New York City (NYC). Here, we investigated the structure of the microbiome and the prevalence of antibiotic resistance genes in raw sewage samples collected from the fourteen NYC Department of Environmental Protection wastewater treatment plants, distributed across the five NYC boroughs. Sewage, a direct output of anthropogenic activity and a reservoir of microbes, provides an ecological niche to examine the spread of antibiotic resistance. Taxonomic diversity analysis revealed a largely similar and stable bacterial population structure across all the samples, which was found to be similar over three time points in an annual cycle, as well as in the five NYC boroughs. All samples were positive for the presence of the seven antibiotic resistance genes tested, based on real-time quantitative PCR assays, with higher levels observed for tetracycline resistance genes at all time points. For five of the seven genes, abundances were significantly higher in May than in February and August. This study provides characteristics of the NYC sewage resistome in the context of the overall bacterial populations. IMPORTANCE Urban sewage or wastewater is a diverse source of bacterial growth, as well as a hot spot for the development of environmental antibiotic resistance, which can in turn influence the health of the residents of the city. As part of a larger study to characterize the urban New York City microbial metagenome, we collected raw sewage samples representing three seasonal time points spanning the five boroughs of NYC and went on to characterize the microbiome and the presence of a range of antibiotic resistance genes. Through this study, we have established a baseline microbial population and antibiotic resistance abundance in NYC sewage which can prove to be very useful in studying the load of antibiotic usage, as well as for developing effective measures in antibiotic stewardship.


2019 ◽  
Author(s):  
Marinelle Rodrigues ◽  
Sara W. McBride ◽  
Karthik Hullahalli ◽  
Kelli L. Palmer ◽  
Breck A. Duerkop

AbstractThe innovation of new therapies to combat multidrug-resistant (MDR) bacteria is being outpaced by the continued rise of MDR bacterial infections. Of particular concern are hospital-acquired infections (HAIs) recalcitrant to antibiotic therapies. The Gram-positive intestinal pathobiontEnterococcus faecalisis associated with HAIs and some strains are MDR. Therefore, novel strategies to controlE. faecalispopulations are needed. We previously characterized anE. faecalisType II CRISPR-Cas system and demonstrated its utility in the sequence-specific removal of antibiotic resistance determinants. Here we present work describing the adaption of this CRISPR-Cas system into a constitutively expressed module encoded on a pheromone-responsive conjugative plasmid that efficiently transfers toE. faecalisfor the selective removal of antibiotic resistance genes. Usingin vitrocompetition assays, we show that these CRISPR-Cas-encoding delivery plasmids, or CRISPR-Cas antimicrobials, can reduce the occurrence of antibiotic resistance in enterococcal populations in a sequence-specific manner. Furthermore, we demonstrate that deployment of CRISPR-Cas antimicrobials in the murine intestine reduces the occurrence of antibiotic-resistantE. faecalisby several orders of magnitude. Finally, we show thatE. faecalisdonor strains harboring CRISPR-Cas antimicrobials are immune to uptake of antibiotic resistance determinantsin vivo. Our results demonstrate that conjugative delivery of CRISPR-Cas antimicrobials may be adaptable for future deployment from probiotic bacteria for exact targeting of defined MDR bacteria or for precision engineering of polymicrobial communities in the mammalian intestine.ImportanceCRISPR-Cas nucleic acid targeting systems hold promise for the amelioration of multidrug-resistant enterococci, yet the utility of such tools in the context of the intestinal environment where enterococci reside is understudied. We describe the development of a CRISPR-Cas antimicrobial, deployed on a conjugative plasmid, for the targeted removal of antibiotic resistance genes from intestinalEnterococcus faecalis. We demonstrate that CRISPR-Cas targeting reduces antibiotic resistance ofE. faecalisby several orders of magnitude in the intestine. Although barriers exist that influence the penetrance of the conjugative CRISPR-Cas antimicrobial among target recipientE. faecaliscells, the removal of antibiotic resistance genes inE. faecalisupon uptake of the CRISPR-Cas antimicrobial is absolute. In addition, cells that obtain the CRISPR-Cas antimicrobial are immunized against the acquisition of new antibiotic resistance genes. This study suggests a potential path toward plasmid based CRISPR-Cas therapies in the intestine.


2021 ◽  
Vol 12 ◽  
Author(s):  
Oliver McNeilly ◽  
Riti Mann ◽  
Mohammad Hamidian ◽  
Cindy Gunawan

The misuse of antibiotics combined with a lack of newly developed ones is the main contributors to the current antibiotic resistance crisis. There is a dire need for new and alternative antibacterial options and nanotechnology could be a solution. Metal-based nanoparticles, particularly silver nanoparticles (NAg), have garnered widespread popularity due to their unique physicochemical properties and broad-spectrum antibacterial activity. Consequently, NAg has seen extensive incorporation in many types of products across the healthcare and consumer market. Despite clear evidence of the strong antibacterial efficacy of NAg, studies have raised concerns over the development of silver-resistant bacteria. Resistance to cationic silver (Ag+) has been recognised for many years, but it has recently been found that bacterial resistance to NAg is also possible. It is also understood that exposure of bacteria to toxic heavy metals like silver can induce the emergence of antibiotic resistance through the process of co-selection. Acinetobacter baumannii is a Gram-negative coccobacillus and opportunistic nosocomial bacterial pathogen. It was recently listed as the “number one” critical level priority pathogen because of the significant rise of antibiotic resistance in this species. NAg has proven bactericidal activity towards A. baumannii, even against strains that display multi-drug resistance. However, despite ample evidence of heavy metal (including silver; Ag+) resistance in this bacterium, combined with reports of heavy metal-driven co-selection of antibiotic resistance, little research has been dedicated to assessing the potential for NAg resistance development in A. baumannii. This is worrisome, as the increasingly indiscriminate use of NAg could promote the development of silver resistance in this species, like what has occurred with antibiotics.


Author(s):  
Marissa Gittrich ◽  
Yunxiao Liu ◽  
Funing Tian ◽  
Audra Crouch ◽  
Ho Bin Jang ◽  
...  

: As antibiotic resistance undermines efforts to treat bacterial infections, phage therapy is being increasingly considered as an alternative in clinical settings and agriculture. However, a major concern in using phages is that pathogens will develop resistance to the phage. Due to the constant evolutionary pressure by phages, bacteria have evolved numerous mechanisms to block infection. If we determine the most common among them, we could use this knowledge to guide phage therapeutics. Here we compile data from 88 peer-reviewed studies where phage resistance was experimentally observed and linked to a bacterial gene, then assessed these data for patterns. In total, 141 host genes were identified to block infection against one or more of 80 phages (representing five families of the Caudovirales) across 16 microbial host genera. These data suggest that bacterial phage resistance is diverse, but even well-studied systems are understudied, and there are gaping holes in our knowledge of phage resistance across lesser-studied regions of microbial and viral sequence space. Fortunately, scalable approaches are newly available that, if broadly adopted, can provide data to power ecosystem-aware models that will guide harvesting natural variation towards designing effective, broadly applicable phage therapy cocktails as an alternative to antibiotics.


2021 ◽  
Vol 6 (4) ◽  
pp. 199-207
Author(s):  
I. I. Fohel ◽  
◽  
M. V. Kryvtsova ◽  
Y. Y. Bugir

Over the last decade, the phenomenon of antibiotic resistance of microorganisms has become a global problem for modern medicine around the world. Bacteria quickly acquire genes of resistance to the action of the antibiotics. Bacterial infections that used to be easy to treat, now, in some cases, can even be life-threatening. Resistant microorganisms pose a danger not only among the adult population but also among the pediatric population. According to the World Health Organization, up to 200,000 newborns die each year from infections caused by antibiotic-resistant microorganisms. Premature babies are at particular risk because their immune systems are still underdeveloped. The use of antibiotics in children should be reasonably approached, as recent studies have shown an increase of the spread of bacteria with resistance genes. Infections caused by resistant microorganisms are more difficult to treat and require special methods and approaches, especially for children, where the choice of antibiotics is already limited. The purpose of the study is to analyze the literature for the current state of the problem of antibiotic resistance, prospects for future development, relevance in pediatric practice. Materials and methods. The research materials are publications of national and foreign authors. Analytical methods were used as main research methods. This article considers the problem of antibiotic resistance, general mechanisms of its formation, research data on the prevalence of circulation of resistant strains in the pediatric population and their role in the initiation of resistant bacterial infections. Conclusion. It is concluded that bacteria insensitive to antibiotics are quite common among the pediatric population and in some cases are life-threatening. This phenomenon requires constant monitoring in order to detect and correctly treat persistent bacterial infections. There are many strains resistant to first- and second-generation antibiotics circulating in children. In some cases, the treatment of certain conditions in pediatrics may lead to the use of reserve antibiotics. Systemic coordinated work around the world and an individual approach in determining the sensitivity of microorganisms to antibiotics in each case can prevent the rapid acquisition of resistance genes by bacteria. It is also necessary to spread information about the threat of antibiotic resistance in order to raise public awareness and counteract the empirical use of antibiotics at home without a prescription. There is also an urgent need to invent new chemical compounds with bactericidal properties as soon as possible


2020 ◽  
Author(s):  
Yan Xu ◽  
Houyu Li ◽  
Rongguang Shi ◽  
Jiapei Lv ◽  
Bihan Li ◽  
...  

Abstract Background: The prevalence of antibiotic resistance genes (ARGs) in animal manure poses threats to the environmental safety. Organic fertilizers fermented by livestock and poultry manure are directly applied to farmland, which would cause the potential outbreak of bacterial resistance in agricultural environment. This study investigated the composition of ARGs in different animal manure and their derived organic fertilizers. Results: Results showed that the abundance of several ARGs, such as sul 2, Tet B-01, Tet G-01 and Tet M-01 in organic fertilizer samples was 12%~96% lower than in animal manure. However, there was an increasing of Tet K and erm C abundance from animal manure to the organic fertilizers. No correlation between ARGs and environmental factors such as pH, TN, antibiotics was observed by Redundancy analysis (RDA). Procrustes analysis revealed the significant correlation between bacterial community structures and the ARGs abundance (r=0.799, p<0.01). Non-metric multidimensional scaling (NMDS) analysis suggested that microorganisms in organic fertilizer may be derived from animal manure. Additional, pathogenic bacteria (especially Actinomadura ) would proliferate rather than decrease from manure to organic fertilizer. Conclusion: Overall, this research suggests that the composting treatment of manure could effectively reduce these ARGs and pathogens,even cause partial ARGs and pathogens proliferation. It also shows that the microorganism might significantly influence ARGs profiles in composting.


2001 ◽  
Vol 22 (12) ◽  
pp. 767-770 ◽  
Author(s):  
Ruben Bromiker ◽  
Ilan Arad ◽  
Ofra Peleg ◽  
Aviya Preminger ◽  
Dan Engelhard

AbstractObjective:To determine the incidence and evaluate the antimicrobial-susceptibility patterns of bacterial infections in our neonatal units.Design:Retrospective surveillance study.Setting:The neonatal units of the Hadassah University Hospitals, Jerusalem, Israel.Patients:All newborns admitted from January 1994 through February 1999.Methods:The records of all patients with positive blood and cerebrospinal fluid cultures were reviewed. Bacteremia was considered early-onset (vertical) when occurring within the first 72 hours of life and late-onset (nosocomial) when occurring later. The prevalence and antibiotic-resistance patterns of vertically transmitted and nosocomially acquired strains were compared and studied over time.Results:219 of 35,691 newborn infants had at least one episode of bacteremia (6.13/1,000 live births). There were 305 identified organisms, of which 21% (1.29/1,000 live births) were considered vertically transmitted and 79% nosocomially acquired. The most common organism causing early-onset disease (29.2%) was group B streptococcus (0.38/1,000 live births), whereas coagulase-negative staphylococci (51%) were the most prevalent in late-onset disease. All gram-positive bacteria were susceptible to vancomycin. Most gram-positive organisms other than staphylococci were susceptible to ampicillin. Gram-negative organisms represented 31% of all isolates. Generally, there was a trend of increasing resistance to commonly used antibiotics among nosocomially acquired gram-negative organisms, compared to those vertically transmitted, with statistically significant differences for ampicillin and mezlocillin (P<.05 andP<.01, respectively). Over the years, a trend toward an increasing resistance to antibiotics was observed among gram-negative organisms.Conclusions:The trend of increasing bacterial resistance to commonly used antibiotics necessitates the implementation of a rational empirical treatment strategy, based on local susceptibility data, reserving certain agents for emerging resistant pathogens.


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