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

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.

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Tea: An anti-bacterial agent against drug resistant bacteria

10.53350/pjmhs2115102506 ◽

2021 ◽

Vol 15 (10) ◽

pp. 2506-2511

Author(s):

Nayyab Sultan ◽

Sabahat Javaid Butt ◽

Wajeeha Mehak ◽

Samreen Qureshi ◽

Syed Hamza Abbas ◽

...

Keyword(s):

Bacterial Infections ◽

Salmonella Typhi ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Klebsiella Pneumonia ◽

Drug Resistant ◽

Antibiotic Resistant ◽

Bacterial Agent ◽

Drug Resistant Bacteria ◽

Scientific World

Antibiotics have played a crucial role in the treatment of bacterial infections. Past few decades are marked with advancement of multidrug resistant (MDR) pathogens, which have endangered antibiotic’s therapeutic efficacy. Scientific world is now struggling with the crisis of MDR pathogens. This supreme matter demands careful attention or otherwise it would jeopardize clinical management of infectious diseases. Implication of alternative approaches can pave a new way in the treatment of these troublesome bacteria. Tea leaves are known to pose antibacterial activity against many pathogenic microorganisms. This review has summarized the antibacterial potential of tea leave’s extracts against resistant bacterial pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Helicobacter pylori, Escherichia coli, Klebsiella pneumonia, Salmonella typhi, Acenitobacter spp, Campylobacter spp. Consumption of natural products such as tea may very well replace, minimize or obliterate this complicated situation. Keywords: Anti-bacterial, Tea, Camellia sinensis, Drug resistant bacteria, Antibiotic resistant bacteria, Synergism, Polyphenols.

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Lysophosphatidylcholine Potentiates Antibacterial Activity of Polymyxin B

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01337-20 ◽

2020 ◽

Vol 64 (12) ◽

Author(s):

Jitender Yadav ◽

Sana Ismaeel ◽

Ayub Qadri

Keyword(s):

Antibacterial Activity ◽

Polymyxin B ◽

Resistant Bacteria ◽

Bacterial Membrane ◽

Gram Negative Bacteria ◽

Drug Resistant ◽

Antibiotic Resistant ◽

Gram Negative ◽

Drug Resistant Bacteria

ABSTRACT Polymyxin B, used to treat infections caused by antibiotic-resistant Gram-negative bacteria, produces nephrotoxicity at its current dosage. We show that a combination of nonbactericidal concentration of this drug and lysophosphatidylcholine (LPC) potently inhibits growth of Salmonella and at least two other Gram-negative bacteria in vitro. This combination makes bacterial membrane porous and causes degradation of DnaK, the regulator of protein folding. Polymyxin B-LPC combination may be an effective and safer regimen against drug-resistant bacteria.

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Profile of antimicrobial resistance in oncologic pediatric patients

Mexican Journal of Medical Research ◽

10.29057/mjmr.v2i4.1812 ◽

2014 ◽

Vol 2 (4) ◽

Author(s):

Mauricio García-Luna ◽

José Antonio Madrid Gómez-Tagle ◽

Jessica P. O’Brien

Keyword(s):

Antimicrobial Resistance ◽

Lymphoblastic Leukemia ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Gram Positive ◽

Gram Negative ◽

E Coli ◽

Development Of Resistance ◽

Drug Resistant Bacteria ◽

Clinical Records

The development of resistance to antibiotics is due to the widespread use of a wide variety of antimicrobials, coupled with the ability of bacteria to acquire and spread resistance and the ability of humans to disseminate them. The possible consequences of antimicrobial resistance leads to greater chances of hospitalization, prolongation of hospital stay and increased mortality. Furthermore, treatment of drug resistant bacteria requires the use of more toxic drugs and more expense for the patient and hospitals. The main objective of the present study was to determine the frequency and nature of antimicrobial resistance of microorganisms in oncologic and hematologic patients at a Mexican Pediatric Hospital. A retrospective, observational, and analytical study was realized, where we reviewed the clinical records of 20 cases. Blood cultures were obtained from the Laboratory of our institution from 2010 to 2011. The data obtained were organized and analyzed. We observed that the E. coli and S. aureus were the bacteria most resistant, showing the same percentage between gram-positive and gram-negative bacteria. The cancer diagnosis most common in our study was acute lymphoblastic leukemia. It may be concluded that multidrug-resistant bacteria in these patients are of a nosocomial origin, without a specific group of germ (gram positive vs. gram negative).

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The Need for New Microbiological Water Quality Criteria

Water Science & Technology ◽

10.2166/wst.1991.0027 ◽

1991 ◽

Vol 24 (2) ◽

pp. 43-48 ◽

Cited By ~ 4

Author(s):

Helmy T. El-Zanfaly

Keyword(s):

Public Health ◽

Water Quality ◽

Drinking Water ◽

Plate Count ◽

Resistant Bacteria ◽

Water Quality Criteria ◽

Antibiotic Resistant Bacteria ◽

Gram Positive ◽

Antibiotic Resistant ◽

Gram Negative

The microbiological criteria for water quality have been directed towards protection of consumers from possible microbial pollution which may cause public health hazards. Therefore, the bacteriological standards for drinking water are based mainly on bacterial indicators. Another problem of prime concern to public health is the presence of antibiotic-resistant bacteria in drinking water Antibiotic–resistant bacteria were found among standard plate count populations of Chlorinated drinking water from two districts in Cairo. Most strains appeared to be ampicillin resistant (89%). Those were followed by sulfaguanidine (78%) and streptomycin (57%). The majority of the tested strains (62.4 to 98%) were multiple antibiotic resistant (MAR). Identification of 363 MAR strains revealed that Gram-positive rods were dominant, while Gram-negative fermentative rods, Gram-positive cocci and Gram-negative nonfermentative rods represent the second, third and fourth group. A total of 101 strains isolated from underground water pumped from three water works in Cairo were classified and tested for their resistance towards four commonly used antibiotics; chloramphenicol, tetracycline, neomycin, penicillin and one chemotherapeutic agent namely sulfanilamide pyrimidine. Results showed that 77, 64 and 32 isolates have resistance towards penicillin, sulfanilamide pyrimidine and tetracycline, respectively. Only 18 and 8 isolates were resistant to chloramphenicol and neomycin, respectively. It was also found that 19 isolates belonging to 6 genera or groups were sensitive towards all of the tested compounds. Therefore, any source of antibiotic~resistant bacteria must be viewed with concern and use of data on MAR bacteria should be made in future water quality deliberations and in regulating effluent quality discharges.

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Overcoming Intrinsic and Acquired Resistance Mechanisms Associated with the Cell Wall of Gram-Negative Bacteria

Antibiotics ◽

10.3390/antibiotics9090623 ◽

2020 ◽

Vol 9 (9) ◽

pp. 623

Author(s):

Rachael E. Impey ◽

Daniel A. Hawkins ◽

J. Mark Sutton ◽

Tatiana P. Soares da Costa

Keyword(s):

Cell Wall ◽

Acquired Resistance ◽

Resistance Mechanisms ◽

Wall Structure ◽

Resistant Bacteria ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Drug Resistant Bacteria ◽

Global Increase ◽

Unique Cell

The global increase in multi-drug-resistant bacteria is severely impacting our ability to effectively treat common infections. For Gram-negative bacteria, their intrinsic and acquired resistance mechanisms are heightened by their unique cell wall structure. The cell wall, while being a target of some antibiotics, represents a barrier due to the inability of most antibacterial compounds to traverse and reach their intended target. This means that its composition and resulting mechanisms of resistance must be considered when developing new therapies. Here, we discuss potential antibiotic targets within the most well-characterised resistance mechanisms associated with the cell wall in Gram-negative bacteria, including the outer membrane structure, porins and efflux pumps. We also provide a timely update on the current progress of inhibitor development in these areas. Such compounds could represent new avenues for drug discovery as well as adjuvant therapy to help us overcome antibiotic resistance.

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Microanatomy of the Periplasm of Bacillus Licheniformis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100065365 ◽

1971 ◽

Vol 29 ◽

pp. 262-263

Author(s):

B.K. Ghosh

Keyword(s):

Cell Wall ◽

Plasma Membrane ◽

Bacillus Licheniformis ◽

External Environment ◽

Permeability Barrier ◽

Periplasmic Space ◽

Modified Technique ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria

Periplasm of bacteria is the space outside the permeability barrier of plasma membrane but enclosed by the cell wall. The contents of this special milieu exterior could be regulated by the plasma membrane from the internal, and by the cell wall from the external environment of the cell. Unlike the gram-negative organism, the presence of this space in gram-positive bacteria is still controversial because it cannot be clearly demonstrated. We have shown the importance of some periplasmic bodies in the secretion of penicillinase from Bacillus licheniformis.In negatively stained specimens prepared by a modified technique (Figs. 1 and 2), periplasmic space (PS) contained two kinds of structures: (i) fibrils (F, 100 Å) running perpendicular to the cell wall from the protoplast and (ii) an array of vesicles of various sizes (V), which seem to have evaginated from the protoplast.

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High frequency of Gram-negative drug-resistant bacteria both in community- and hospital-acquired bloodstream infections (BSI) in a hospital setting from northern Italy

10.26226/morressier.56d6be74d462b80296c974b5 ◽

2016 ◽

Author(s):

Ottavia Viganò

Keyword(s):

High Frequency ◽

Hospital Setting ◽

Bloodstream Infections ◽

Northern Italy ◽

Resistant Bacteria ◽

Drug Resistant ◽

Gram Negative ◽

Drug Resistant Bacteria ◽

Hospital Acquired

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Gram-positive bacteria cell wall-derived lipoteichoic acid induces inflammatory alveolar bone loss through prostaglandin E production in osteoblasts

Scientific Reports ◽

10.1038/s41598-021-92744-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tsukasa Tominari ◽

Ayumi Sanada ◽

Ryota Ichimaru ◽

Chiho Matsumoto ◽

Michiko Hirata ◽

...

Keyword(s):

Cell Wall ◽

Bone Loss ◽

Alveolar Bone ◽

Osteoclast Differentiation ◽

Lipoteichoic Acid ◽

Alveolar Bone Loss ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria

AbstractPeriodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE2 accompanying the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts. The addition of indomethacin effectively blocked the LTA-induced osteoclast differentiation by suppressing the production of PGE2. Using ex vivo organ cultures of mouse alveolar bone, we found that LTA induced alveolar bone resorption and that this was suppressed by indomethacin. In an experimental model of periodontitis, LTA was locally injected into the mouse lower gingiva, and we clearly detected alveolar bone destruction using 3D-μCT. We herein demonstrate a new concept indicating that Gram-positive bacteria in addition to Gram-negative bacteria are associated with the progression of periodontal bone loss.

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