scholarly journals Sequence-function Relationships in Phage-encoded Bacterial Cell Wall Lytic Enzymes and their Implications for Phage-derived Products Design

2021 ◽  
Author(s):  
Roberto Vázquez ◽  
Ernesto García ◽  
Pedro García
Keyword(s):  
Cell Wall ◽  
Physicochemical Properties ◽  
Current Literature ◽  
Bacterial Infections ◽  
Relevant Information ◽  
Resistant Bacteria ◽  
Lytic Enzymes ◽  
Net Charge ◽  
Aliphatic Index ◽  
Phage Lysins

Phage (endo)lysins are thought to be a viable alternative to usual antibiotic chemotherapy to fight resistant bacterial infections. However, a landscape view of lysins’ structure and properties regarding their function, with an applied focus, is somewhat lacking. Current literature suggests that specific features typical of lysins from phages infecting Gram-negative bacteria (G−) (higher net charge, amphipathic helices) are responsible for improved interaction with the G− envelope. Such antimicrobial peptide (AMP)-like elements are also of interest for antimicrobial molecules design. Thus, this study aims to provide an updated view on the primary structural landscape of phage lysins to clarify the evolutionary importance of several sequence-predicted properties, particularly for the interaction with the G− surface. A database of 2,182 lysin sequences was compiled, containing relevant information such as domain architectures, data on the phages’ host bacteria, and sequence-predicted physicochemical properties. Based on such classifiers, an investigation of the differential appearance of certain features was conducted. Such analyses revealed different lysin architectural variants that are preferably found in phages infecting certain bacterial hosts. Particularly, some physicochemical properties (higher net charge, hydrophobicity, hydrophobic moment, and aliphatic index) were associated with G− phage lysins, appearing specifically at their C-terminal end. Evidence on the remarkable genetic specialization of lysins regarding the features of the bacterial hosts has been provided, specifically supporting the nowadays common hypothesis that lysins from G− usually contain AMP-like regions. IMPORTANCE Phage-encoded lytic enzymes, also called lysins, are one of the most promising alternatives to common antibiotics. The potential of lysins as novel antimicrobials to tackle antibiotic-resistant bacteria not only arises from features such as a lower chance to provoke resistance, but also from their versatility as synthetic biology parts. Functional modules derived from lysins are currently being used for the design of novel antimicrobials with desired properties. This study provides a view of the lysins diversity landscape by examining a set of phage lysin genes. This way, we have uncovered the fundamental differences between the lysins from phages that infect bacteria with different superficial architectures, and, thus, also the reach of their specialization regarding cell wall structures. These results provide clarity and evidence to sustain some of the common hypotheses in current literature, as well as make available an updated and characterized database of lysins sequences for further developments.

scholarly journals Sequence-function Relationships in Phage-encoded Bacterial Cell Wall Lytic Enzymes and their Implications for Phage-derived Products Design

2021 ◽  
Author(s):  
Roberto Vázquez ◽  
Ernesto García ◽  
Pedro García
Keyword(s):  
Cell Wall ◽  
Physicochemical Properties ◽  
Current Literature ◽  
Bacterial Infections ◽  
Relevant Information ◽  
Resistant Bacteria ◽  
Lytic Enzymes ◽  
Net Charge ◽  
Aliphatic Index ◽  
Phage Lysins

ABSTRACTPhage (endo)lysins are thought to be a viable alternative to usual antibiotic chemotherapy to fight resistant bacterial infections. However, a landscape view of lysins’ structure and properties regarding their function, with an applied focus, is somewhat lacking. Current literature suggests that specific features typical of lysins from phages infecting Gram-negative bacteria (G−) (higher net charge, amphipathic helices) are responsible for an improved interaction with G− envelope. Such antimicrobial peptide (AMP)-like elements are also of interest for antimicrobial molecules design. Thus, this study aims to provide an updated view on the primary structural landscape of phage lysins to clarify the evolutionary importance of several sequence-predicted properties, particularly for the interaction with the G− surface. A database of 2,182 lysin sequences was compiled, containing relevant information such as domain architectures, data on the phages’ host bacteria and sequence-predicted physicochemical properties. Based on such classifiers, an investigation on the differential appearance of certain features was conducted. Such analyses revealed different lysin architectural variants that are preferably found in phages infecting certain bacterial hosts. Particularly, some physicochemical properties (higher net charge, hydrophobicity, hydrophobic moment and aliphatic index) were associated to G− phage lysins, appearing specifically at their C-terminal end. Evidences on the remarkable genetic specialization of lysins regarding the features of the bacterial hosts have been provided, specifically supporting the nowadays common hypothesis that lysins from G− usually contain AMP-like regions.IMPORTANCEPhage-encoded lytic enzymes, also called lysins, are one of the most promising alternatives to common antibiotics. The lysins potential as novel antimicrobials to tackle antibiotic-resistant bacteria not only arises from features such as a lower chance to provoke resistance, but also from their versatility as synthetic biology parts. Functional modules derived from lysins are currently being used for the design of novel antimicrobials with desired properties. This study provides a view of the lysins diversity landscape by examining a set of phage lysin genes. This way, we have uncovered the fundamental differences between the lysins from phages that infect bacteria with different superficial architectures, and, thus, also the reach of their specialization regarding cell wall structures. These results provide clarity and evidences to sustain some of the common hypothesis in current literature, as well as make available an updated and characterized database of lysins sequences for further developments.

scholarly journals Review on Multiple Facets of Drug Resistance: A Rising Challenge in the 21st Century

2021 ◽  
Vol 11 (4) ◽  
pp. 197-214
Author(s):  
Mousumi Saha ◽  
Agniswar Sarkar
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
In Silico Analysis ◽  
Relevant Information ◽  
High Rate ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Potential Threat

With the advancements of science, antibiotics have emerged as an amazing gift to the human and animal healthcare sectors for the treatment of bacterial infections and other diseases. However, the evolution of new bacterial strains, along with excessive use and reckless consumption of antibiotics have led to the unfolding of antibiotic resistances to an excessive level. Multidrug resistance is a potential threat worldwide, and is escalating at an extremely high rate. Information related to drug resistance, and its regulation and control are still very little. To interpret the onset of antibiotic resistances, investigation on molecular analysis of resistance genes, their distribution and mechanisms are urgently required. Fine-tuned research and resistance profile regarding ESKAPE pathogen is also necessary along with other multidrug resistant bacteria. In the present scenario, the interaction of bacterial infections with SARS-CoV-2 is also crucial. Tracking and in-silico analysis of various resistance mechanisms or gene/s are crucial for overcoming the problem, and thus, the maintenance of relevant databases and wise use of antibiotics should be promoted. Creating awareness of this critical situation among individuals at every level is important to strengthen the fight against this fast-growing calamity. The review aimed to provide detailed information on antibiotic resistance, its regulatory molecular mechanisms responsible for the resistance, and other relevant information. In this article, we tried to focus on the correlation between antimicrobial resistance and the COVID-19 pandemic. This study will help in developing new interventions, potential approaches, and strategies to handle the complexity of antibiotic resistance and prevent the incidences of life-threatening infections.

From endolysins to Artilysin®s: novel enzyme-based approaches to kill drug-resistant bacteria

2016 ◽  
Vol 44 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Hans Gerstmans ◽  
Lorena Rodríguez-Rubio ◽  
Rob Lavigne ◽  
Yves Briers
Keyword(s):  
Cell Wall ◽  
Resistant Bacteria ◽  
Infection Cycle ◽  
Lytic Enzymes ◽  
Gram Positive ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Bacterial Agent ◽  
Drug Resistant Bacteria ◽  
Pass Through

One of the last untapped reservoirs in nature for the identification of new anti-microbials is bacteriophages, the natural killers of bacteria. Lytic bacteriophages encode peptidoglycan (PG) lytic enzymes able to degrade the PG layer in different steps of their infection cycle. Endolysins degrade the bacterial cell wall at the end of the infection cycle, causing lysis of the host to release the viral progeny. Recombinant endolysins have been successfully applied as anti-bacterial agent against antibiotic-resistant Gram-positive pathogens. This has boosted the study of these enzymes as new anti-microbials in different fields (e.g. medical, food technology). A key example is the recent development of endolysin-based anti-bacterials against Gram-negative pathogens in which the exogenous application of endolysins is hindered by the outer membrane (OM). These novel anti-microbials, termed Artilysin®s, are able to pass through the OM and reach the PG where they exert their action. In addition, mycobacteria whose cell wall is structurally different from both Gram-positive and Gram-negative bacteria have also been reported to be inhibited by mycobacteriophage-encoded endolysins. Endolysins and endolysin-based anti-microbials can be considered as ideal candidates for an alternative to antibiotics for several reasons: (1) their unique mode of action and activity against bacterial persisters (independent of an active host metabolism), (2) their selective activity against both Gram-positive and Gram-negative pathogens (including antibiotic resistant strains) and mycobacteria, (3) the limited resistance development reported so far. The present review summarizes and discusses the potential applications of endolysins as new anti-microbials.

A Computational Method for the Identification of Endolysins and Autolysins

2020 ◽  
Vol 27 (4) ◽  
pp. 329-336 ◽  
Author(s):  
Lei Xu ◽  
Guangmin Liang ◽  
Baowen Chen ◽  
Xu Tan ◽  
Huaikun Xiang ◽  
...  
Keyword(s):  
Support Vector Machine ◽  
Cell Wall ◽  
Experimental Results ◽  
Computational Method ◽  
Lytic Enzyme ◽  
Support Vector ◽  
Lytic Enzymes ◽  
Data Set ◽  
Optimal Feature ◽  
Better Than

Background: Cell lytic enzyme is a kind of highly evolved protein, which can destroy the cell structure and kill the bacteria. Compared with antibiotics, cell lytic enzyme will not cause serious problem of drug resistance of pathogenic bacteria. Thus, the study of cell wall lytic enzymes aims at finding an efficient way for curing bacteria infectious. Compared with using antibiotics, the problem of drug resistance becomes more serious. Therefore, it is a good choice for curing bacterial infections by using cell lytic enzymes. Cell lytic enzyme includes endolysin and autolysin and the difference between them is the purpose of the break of cell wall. The identification of the type of cell lytic enzymes is meaningful for the study of cell wall enzymes. Objective: In this article, our motivation is to predict the type of cell lytic enzyme. Cell lytic enzyme is helpful for killing bacteria, so it is meaningful for study the type of cell lytic enzyme. However, it is time consuming to detect the type of cell lytic enzyme by experimental methods. Thus, an efficient computational method for the type of cell lytic enzyme prediction is proposed in our work. Method: We propose a computational method for the prediction of endolysin and autolysin. First, a data set containing 27 endolysins and 41 autolysins is built. Then the protein is represented by tripeptides composition. The features are selected with larger confidence degree. At last, the classifier is trained by the labeled vectors based on support vector machine. The learned classifier is used to predict the type of cell lytic enzyme. Results: Following the proposed method, the experimental results show that the overall accuracy can attain 97.06%, when 44 features are selected. Compared with Ding's method, our method improves the overall accuracy by nearly 4.5% ((97.06-92.9)/92.9%). The performance of our proposed method is stable, when the selected feature number is from 40 to 70. The overall accuracy of tripeptides optimal feature set is 94.12%, and the overall accuracy of Chou's amphiphilic PseAAC method is 76.2%. The experimental results also demonstrate that the overall accuracy is improved by nearly 18% when using the tripeptides optimal feature set. Conclusion: The paper proposed an efficient method for identifying endolysin and autolysin. In this paper, support vector machine is used to predict the type of cell lytic enzyme. The experimental results show that the overall accuracy of the proposed method is 94.12%, which is better than some existing methods. In conclusion, the selected 44 features can improve the overall accuracy for identification of the type of cell lytic enzyme. Support vector machine performs better than other classifiers when using the selected feature set on the benchmark data set.

Microbiome in Chronic Obstructive Pulmonary Disease: Role of Natural Products Against Microbial Pathogens

2020 ◽  
Vol 27 (18) ◽  
pp. 2931-2948
Author(s):  
Alessia Santoro ◽  
Carlo Tomino ◽  
Giulia Prinzi ◽  
Vittorio Cardaci ◽  
Massimo Fini ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Microbial Communities ◽  
Pulmonary Disease ◽  
Bacterial Infections ◽  
Microbial Pathogens ◽  
Resistant Bacteria ◽  
Chronic Obstructive ◽  
Detection Rates ◽  
Obstructive Pulmonary Disease ◽  
Lung Microbiome

The “microbiome” is the operative term to refer to a collection of all taxa constituting microbial communities, such as bacteria, archaea, fungi and protists (originally microbiota). The microbiome consists of the indigenous microbial communities and of the host environment that they inhabit. Actually, it has been shown that there is a close relationship between the microbiome and human health and disease condition. Although, initially, the lung was considered sterile, actually, the existence of a healthy lung microbiome is usually accepted. Lung microbiome changes are reported in Chronic Obstructive Pulmonary Disease (COPD) and in its exacerbation. Viral and bacterial infections of the respiratory system are a major cause of COPD exacerbations (AECOPD) leading to increased local and systemic inflammation. Detection rates of virus in AECOPD are variable between 25-62% according to the detection method. The study of human airway and lung disease virome is quite recent and still very limited. The purpose of this review is to summarize recent findings on the lung microbiome composition with a special emphasis on virome in COPD and in AECOPD. Some drugs of natural origins active against resistant bacteria and virus are described.

Development of Peptides that Inhibit Aminoglycoside-Modifying Enzymes and β-Lactamases for Control of Resistant Bacteria

2020 ◽  
Vol 21 (10) ◽  
pp. 1011-1026
Author(s):  
Bruna O. Costa ◽  
Marlon H. Cardoso ◽  
Octávio L. Franco
Keyword(s):  
Drug Target ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Treatment Strategies ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Specific Chemical ◽  
Target Interaction ◽  
Multiresistant Bacteria ◽  
Acute Bacterial Infections

: Aminoglycosides and β-lactams are the most commonly used antimicrobial agents in clinical practice. This occurs because they are capable of acting in the treatment of acute bacterial infections. However, the effectiveness of antibiotics has been constantly threatened due to bacterial pathogens producing resistance enzymes. Among them, the aminoglycoside-modifying enzymes (AMEs) and β-lactamase enzymes are the most frequently reported resistance mechanisms. AMEs can inactivate aminoglycosides by adding specific chemical molecules in the compound, whereas β-lactamases hydrolyze the β-lactams ring, preventing drug-target interaction. Thus, these enzymes provide a scenario of multidrug-resistance and a significant threat to public health at a global level. In response to this challenge, in recent decades, several studies have focused on the development of inhibitors that can restore aminoglycosides and β-lactams activity. In this context, peptides appear as a promising approach in the field of inhibitors for future antibacterial therapies, as multiresistant bacteria may be susceptible to these molecules. Therefore, this review focused on the most recent findings related to peptide-based inhibitors that act on AMEs and β-lactamases, and how these molecules could be used for future treatment strategies.

Re-challenging antibiotic resistance with Daniel Berman

2020 ◽  
Author(s):  
Daniel Berman
Keyword(s):  
Bacterial Infections ◽  
Point Of Care ◽  
Healthcare Setting ◽  
Rapid Diagnostic Tests ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Global Threat ◽  
The Right ◽  
Point Of Care Tests

How can we prevent the rise of resistance to antibiotics? In this video, Daniel Berman,  Nesta Challenges, discusses the global threat of AMR and how prizes like the Longitude Prize can foster the development of rapid diagnostic tests for bacterial infections, helping to contribute towards reducing the global threat of drug resistant bacteria. Daniel outlines how accelerating the development of rapid point-of-care tests will ensure that bacterial infections are treated with the most appropriate antibiotic, at the right time and in the right healthcare setting.

scholarly journals Antibiotic-Resistant Bacteria in Clams—A Study on Mussels in the River Rhine

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 571
Author(s):  
Nicole Zacharias ◽  
Iris Löckener ◽  
Sarah M. Essert ◽  
Esther Sib ◽  
Gabriele Bierbaum ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Sewage Treatment ◽  
Sewage Treatment Plant ◽  
Treatment Plant ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
River Rhine ◽  
Antibiotic Resistant Bacteria ◽  
Surrounding Water ◽  
Antibiotic Resistant

Bacterial infections have been treated effectively by antibiotics since the discovery of penicillin in 1928. A worldwide increase in the use of antibiotics led to the emergence of antibiotic resistant strains in almost all bacterial pathogens, which complicates the treatment of infectious diseases. Antibiotic-resistant bacteria play an important role in increasing the risk associated with the usage of surface waters (e.g., irrigation, recreation) and the spread of the resistance genes. Many studies show that important pathogenic antibiotic-resistant bacteria can enter the environment by the discharge of sewage treatment plants and combined sewage overflow events. Mussels have successfully been used as bio-indicators of heavy metals, chemicals and parasites; they may also be efficient bio-indicators for viruses and bacteria. In this study an influence of the discharge of a sewage treatment plant could be shown in regard to the presence of E. coli in higher concentrations in the mussels downstream the treatment plant. Antibiotic-resistant bacteria, resistant against one or two classes of antibiotics and relevance for human health could be detected in the mussels at different sampling sites of the river Rhine. No multidrug-resistant bacteria could be isolated from the mussels, although they were found in samples of the surrounding water body.

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