-
1.
Deploying Viruses against Phytobacteria: Potential Use of Phage Cocktails as a Multifaceted Approach to Combat Resistant Bacterial Plant Pathogens.
Farooq, T, Hussain, MD, Shakeel, MT, Tariqjaveed, M, Aslam, MN, Naqvi, SAH, Amjad, R, Tang, Y, She, X, He, Z
Viruses. 2022;(2)
Abstract
Plants in nature are under the persistent intimidation of severe microbial diseases, threatening a sustainable food production system. Plant-bacterial pathogens are a major concern in the contemporary era, resulting in reduced plant growth and productivity. Plant antibiotics and chemical-based bactericides have been extensively used to evade plant bacterial diseases. To counteract this pressure, bacteria have evolved an array of resistance mechanisms, including innate and adaptive immune systems. The emergence of resistant bacteria and detrimental consequences of antimicrobial compounds on the environment and human health, accentuates the development of an alternative disease evacuation strategy. The phage cocktail therapy is a multidimensional approach effectively employed for the biocontrol of diverse resistant bacterial infections without affecting the fauna and flora. Phages engage a diverse set of counter defense strategies to undermine wide-ranging anti-phage defense mechanisms of bacterial pathogens. Microbial ecology, evolution, and dynamics of the interactions between phage and plant-bacterial pathogens lead to the engineering of robust phage cocktail therapeutics for the mitigation of devastating phytobacterial diseases. In this review, we highlight the concrete and fundamental determinants in the development and application of phage cocktails and their underlying mechanism, combating resistant plant-bacterial pathogens. Additionally, we provide recent advances in the use of phage cocktail therapy against phytobacteria for the biocontrol of devastating plant diseases.
-
2.
Effect of antibiotics in preventing hospitalizations from respiratory tract infections in children with Down syndrome.
Manikam, L, Lakhanpaul, M, Schilder, AGM, Littlejohns, P, Cupp, MA, Alexander, EC, Hayward, A
Pediatric pulmonology. 2021;(1):171-178
Abstract
BACKGROUND Children with Down syndrome (DS) are at high risk of respiratory tract infections (RTIs) due to anatomical variations, comorbidities, and immune system immaturity. Evidence on interventions to reduce this risk is incomplete. This study aims to quantify the effect of antibiotics prescribed for RTIs in primary care on the subsequent risk of RTI-related hospitalization for children with DS versus controls. METHODS We conducted a retrospective cohort study of 992 children with DS and 4874 controls managed by UK National Health Service General Practitioners (GPs) and hospitals as identified in CALIBER (Clinical disease research using LInked Bespoke studies and Electronic health Records), 1997-2010. Univariate and multivariate logistic regression were undertaken. RESULTS In children with DS, the prescription of antibiotics following an RTI-related GP consultation did not significantly reduce the risk of RTI-related hospitalization in the subsequent 28 days (risk with antibiotics, 1.8%; without, 2.5%; risk ratio, 0.699; 95% confidence interval, 0.471-1.036). Subgroup analyses showed a risk reduction only in infants with DS, after adjustment for covariates. There was no reduction in risk for controls, overall or across subgroups. CONCLUSIONS In conclusion, while prescription of antibiotics following RTI-related GP consultations were effective for infants with DS in reducing subsequent RTI-related hospitalization, this was not the case for older children with DS. We would encourage further high-quality cohort and randomized controlled trials to interrogate this finding, and to examine the impact of antibiotics on other endpoints, including symptom duration.
-
3.
Emerging role of ferrous iron in bacterial growth and host-pathogen interaction: New tools for chemical (micro)biology and antibacterial therapy.
Gonciarz, RL, Renslo, AR
Current opinion in chemical biology. 2021;:170-178
-
-
Free full text
-
Abstract
Chemical tools capable of detecting ferrous iron with oxidation-state specificity have only recently become available. Coincident with this development in chemical biology has been increased study and appreciation for the importance of ferrous iron during infection and more generally in host-pathogen interaction. Some of the recent findings are surprising and challenge long-standing assumptions about bacterial iron homeostasis and the innate immune response to infection. Here, we review these recent developments and their implications for antibacterial therapy.
-
4.
Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants.
Russell, JT, Lauren Ruoss, J, de la Cruz, D, Li, N, Bazacliu, C, Patton, L, McKinley, KL, Garrett, TJ, Polin, RA, Triplett, EW, et al
Scientific reports. 2021;(1):1943
Abstract
Antibiotic use in neonates can have detrimental effects on the developing gut microbiome, increasing the risk of morbidity. A majority of preterm neonates receive antibiotics after birth without clear evidence to guide this practice. Here microbiome, metabolomic, and immune marker results from the routine early antibiotic use in symptomatic preterm Neonates (REASON) study are presented. The REASON study is the first trial to randomize symptomatic preterm neonates to receive or not receive antibiotics in the first 48 h after birth. Using 16S rRNA sequencing of stool samples collected longitudinally for 91 neonates, the effect of such antibiotic use on microbiome diversity is assessed. The results illustrate that type of nutrition shapes the early infant gut microbiome. By integrating data for the gut microbiome, stool metabolites, stool immune markers, and inferred metabolic pathways, an association was discovered between Veillonella and the neurotransmitter gamma-aminobutyric acid (GABA). These results suggest early antibiotic use may impact the gut-brain axis with the potential for consequences in early life development, a finding that needs to be validated in a larger cohort.Trial Registration This project is registered at clinicaltrials.gov under the name "Antibiotic 'Dysbiosis' in Preterm Infants" with trial number NCT02784821.
-
5.
Adjunctive treatments for the management of septic shock - a narrative review of the current evidence.
Donovan, K, Shah, A, Day, J, McKechnie, SR
Anaesthesia. 2021;(9):1245-1258
-
-
Free full text
-
Abstract
Septic shock is a leading cause of death and morbidity worldwide. The cornerstones of management include prompt identification of sepsis, early initiation of antibiotic therapy, adequate fluid resuscitation and organ support. Over the past two decades, there have been considerable improvements in our understanding of the pathophysiology of sepsis and the host response, including regulation of inflammation, endothelial disruption and impaired immunity. This has offered opportunities for innovative adjunctive treatments such as vitamin C, corticosteroids and beta-blockers. Some of these approaches have shown promising results in early phase trials in humans, while others, such as corticosteroids, have been tested in large, international, multicentre randomised controlled trials. Contemporary guidelines make a weak recommendation for the use of corticosteroids to reduce mortality in sepsis and septic shock. Vitamin C, despite showing initial promise in observational studies, has so far not been shown to be clinically effective in randomised trials. Beta-blocker therapy may have beneficial cardiac and non-cardiac effects in septic shock, but there is currently insufficient evidence to recommend their use for this condition. The results of ongoing randomised trials are awaited. Crucial to reducing heterogeneity in the trials of new sepsis treatments will be the concept of enrichment, which refers to the purposive selection of patients with clinical and biological characteristics that are likely to be responsive to the intervention being tested.
-
6.
An Overview of Ozone Therapy for Treating Foot Ulcers in Patients With Diabetes.
Wen, Q, Chen, Q
The American journal of the medical sciences. 2020;(2):112-119
Abstract
Diabetic foot ulcer (DFU) is one of the most common and severe complications of diabetes mellitus, which is becoming increasingly prevalent throughout the world, with high mortality and morbidity. Because of the complex pathophysiological processes involved, DFU is difficult to treat effectively with traditional therapies. Ozone therapy, an emerging method, has been reported as potentially beneficial for closure of DFUs and may gradually move to the forefront of clinical practice. Possible mechanisms of action include antioxidant capacity, pathogen inactivation, vascular and endogenous growth factor modulation, and immune system activation. However, some researchers are skeptical about its safety, and clinical trials are lacking. This article reviews the current research and application of ozone therapy for DFUs.
-
7.
Alterocin, an Antibiofilm Protein Secreted by Pseudoalteromonas sp. Strain 3J6.
Jouault, A, Gobet, A, Simon, M, Portier, E, Perennou, M, Corre, E, Gaillard, F, Vallenet, D, Michel, G, Fleury, Y, et al
Applied and environmental microbiology. 2020;(20)
-
-
Free full text
-
Abstract
We sought to identify and study the antibiofilm protein secreted by the marine bacterium Pseudoalteromonas sp. strain 3J6. The latter is active against marine and terrestrial bacteria, including Pseudomonas aeruginosa clinical strains forming different biofilm types. Several amino acid sequences were obtained from the partially purified antibiofilm protein, named alterocin. The Pseudoalteromonas sp. 3J6 genome was sequenced, and a candidate alt gene was identified by comparing the genome-encoded proteins to the sequences from purified alterocin. Expressing the alt gene in another nonactive Pseudoalteromonas sp. strain, 3J3, demonstrated that it is responsible for the antibiofilm activity. Alterocin is a 139-residue protein that includes a predicted 20-residue signal sequence, which would be cleaved off upon export by the general secretion system. No sequence homology was found between alterocin and proteins of known functions. The alt gene is not part of an operon and adjacent genes do not seem related to alterocin production, immunity, or regulation, suggesting that these functions are not fulfilled by devoted proteins. During growth in liquid medium, the alt mRNA level peaked during the stationary phase. A single promoter was experimentally identified, and several inverted repeats could be binding sites for regulators. alt genes were found in about 30% of the Pseudoalteromonas genomes and in only a few instances of other marine bacteria of the Hahella and Paraglaciecola genera. Comparative genomics yielded the hypothesis that alt gene losses occurred within the Pseudoalteromonas genus. Overall, alterocin is a novel kind of antibiofilm protein of ecological and biotechnological interest.IMPORTANCE Biofilms are microbial communities that develop on solid surfaces or interfaces and are detrimental in a number of fields, including for example food industry, aquaculture, and medicine. In the latter, antibiotics are insufficient to clear biofilm infections, leading to chronic infections such as in the case of infection by Pseudomonas aeruginosa of the lungs of cystic fibrosis patients. Antibiofilm molecules are thus urgently needed to be used in conjunction with conventional antibiotics, as well as in other fields of application, especially if they are environmentally friendly molecules. Here, we describe alterocin, a novel antibiofilm protein secreted by a marine bacterium belonging to the Pseudoalteromonas genus, and its gene. Alterocin homologs were found in about 30% of Pseudoalteromonas strains, indicating that this new family of antibiofilm proteins likely plays an important albeit nonessential function in the biology of these bacteria. This study opens up the possibility of a variety of applications.
-
8.
Understanding the impact of antibiotic perturbation on the human microbiome.
Schwartz, DJ, Langdon, AE, Dantas, G
Genome medicine. 2020;(1):82
Abstract
The human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome's ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.
-
9.
Molecular Structure and Functional Analysis of Pyocin S8 from Pseudomonas aeruginosa Reveals the Essential Requirement of a Glutamate Residue in the H-N-H Motif for DNase Activity.
Turano, H, Gomes, F, Domingos, RM, Degenhardt, MFS, Oliveira, CLP, Garratt, RC, Lincopan, N, Netto, LES
Journal of bacteriology. 2020;(21)
-
-
Free full text
-
Abstract
Multidrug resistance (MDR) is a serious threat to public health, making the development of new antimicrobials an urgent necessity. Pyocins are protein antibiotics produced by Pseudomonas aeruginosa strains to kill closely related cells during intraspecific competition. Here, we report an in-depth biochemical, microbicidal, and structural characterization of a new S-type pyocin, named S8. Initially, we described the domain organization and secondary structure of S8. Subsequently, we observed that a recombinant S8 composed of the killing subunit in complex with the immunity (ImS8) protein killed the strain PAO1. Furthermore, mutation of a highly conserved glutamic acid to alanine (Glu100Ala) completely inhibited this antimicrobial activity. The integrity of the H-N-H motif is probably essential in the killing activity of S8, as Glu100 is a highly conserved residue of this motif. Next, we observed that S8 is a metal-dependent endonuclease, as EDTA treatment abolished its ability to cleave supercoiled pUC18 plasmid. Supplementation of apo S8 with Ni2+ strongly induced this DNase activity, whereas Mn2+ and Mg2+ exhibited moderate effects and Zn2+ was inhibitory. Additionally, S8 bound Zn2+ with a higher affinity than Ni2+ and the Glu100Ala mutation decreased the affinity of S8 for these metals, as shown by isothermal titration calorimetry (ITC). Finally, we describe the crystal structure of the Glu100Ala S8 DNase-ImS8 complex at 1.38 Å, which gave us new insights into the endonuclease activity of S8. Our results reinforce the possibility of using pyocin S8 as an alternative therapy for infections caused by MDR strains, while leaving commensal human microbiota intact.IMPORTANCE Pyocins are proteins produced by Pseudomonas aeruginosa strains that participate in intraspecific competition and host-pathogen interactions. They were first described in the 1950s and since then have gained attention as possible new antibiotics. However, there is still only scarce information about the molecular mechanisms by which these molecules induce cell death. Here, we show that the metal-dependent endonuclease activity of pyocin S8 is involved with its antimicrobial action against strain PAO1. We also describe that this killing activity is dependent on a conserved Glu residue within the H-N-H motif. The potency and selectivity of pyocin S8 toward a narrow spectrum of P. aeruginosa strains make this protein an attractive antimicrobial alternative for combatting MDR strains, while leaving commensal human microbiota intact.
-
10.
Iron Metabolism at the Interface between Host and Pathogen: From Nutritional Immunity to Antibacterial Development.
Marchetti, M, De Bei, O, Bettati, S, Campanini, B, Kovachka, S, Gianquinto, E, Spyrakis, F, Ronda, L
International journal of molecular sciences. 2020;(6)
Abstract
Nutritional immunity is a form of innate immunity widespread in both vertebrates and invertebrates. The term refers to a rich repertoire of mechanisms set up by the host to inhibit bacterial proliferation by sequestering trace minerals (mainly iron, but also zinc and manganese). This strategy, selected by evolution, represents an effective front-line defense against pathogens and has thus inspired the exploitation of iron restriction in the development of innovative antimicrobials or enhancers of antimicrobial therapy. This review focuses on the mechanisms of nutritional immunity, the strategies adopted by opportunistic human pathogen Staphylococcus aureus to circumvent it, and the impact of deletion mutants on the fitness, infectivity, and persistence inside the host. This information finally converges in an overview of the current development of inhibitors targeting the different stages of iron uptake, an as-yet unexploited target in the field of antistaphylococcal drug discovery.