Chemical Biology Tools for Modulating and Visualizing Gram-Negative Bacterial Surface Polysaccharides

Author(s):  
Meng Zheng ◽  
Maggie Zheng ◽  
Samuel Epstein ◽  
Alexa P. Harnagel ◽  
Hanee Kim ◽  
...  

2021 ◽  
Author(s):  
Xukai Jiang ◽  
Nitin A. Patil ◽  
Mohammad A. K. Azad ◽  
Hasini Wickremasinghe ◽  
Heidi Yu ◽  
...  

Multidrug-resistant Gram-negative bacteria have been an urgent threat to global public health. Novel antibiotics are desperately needed to combat these 'superbugs'.



1958 ◽  
Vol 4 (2) ◽  
pp. 65-71 ◽  
Author(s):  
Thomas D. Brock

The bacteriostatic and bactericidal effects of salmine on various bacteria have been studied. Salmine has more bacteriostatic activity against Gram-positive than against Gram-negative bacteria. It is bactericidal in water but not in broth, and this bactericidal action occurs against both Gram-positive and Gram-negative bacteria. It has been shown that salmine causes agglutination of washed suspensions of certain bacteria and this agglutination is not correlated directly with the Gram stain. Salmine causes an increase in the turbidity of washed cells of all bacteria, Gram-positive and Gram-negative, and differs in this respect from the solutes sodium chloride and glucose, which affect only Gram-negative species.A comparison has been made of the effects of salmine and polymyxin and it has been concluded that salmine may also act by attachment to the bacterial surface.



2021 ◽  
Vol 12 ◽  
Author(s):  
Roberto Vázquez ◽  
Sofía Blanco-Gañán ◽  
Susana Ruiz ◽  
Pedro García

Phage (endo)lysins are nowadays one of the most promising ways out of the current antibiotic resistance crisis. Either as sole therapeutics or as a complement to common antibiotic chemotherapy, lysins are already entering late clinical phases to get regulatory agencies’ authorization. Even the old paradigm of the inability of lysins to attack Gram-negative bacteria from without has already been overcome in a variety of ways: either by engineering approaches or investigating the natural mechanisms by which some wild-type lysins are able to interact with the bacterial surface. Such inherent ability of some lysins has been linked to antimicrobial peptide (AMP)-like regions, which are, on their own, a significant source for novel antimicrobials. Currently, though, many of the efforts for searching novel lysin-based antimicrobial candidates rely on experimental screenings. In this work, we have bioinformatically analyzed the C-terminal end of a collection of lysins from phages infecting the Gram-negative genus Pseudomonas. Through the computation of physicochemical properties, the probability of such regions to be an AMP was estimated by means of a predictive k-nearest neighbors (kNN) model. This way, a subset of putatively membrane-interacting lysins was obtained from the original database. Two of such candidates (named Pae87 and Ppl65) were prospectively tested in terms of muralytic, bacteriolytic, and bactericidal activity. Both of them were found to possess an activity against Pseudomonas aeruginosa and other Gram-negative bacterial pathogens, implying that the prediction of AMP-like regions could be a useful approach toward the mining of phage lysins to design and develop antimicrobials or antimicrobial parts for further engineering.



mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Carrie F. Coggon ◽  
Andrew Jiang ◽  
Kelvin G. K. Goh ◽  
Ian R. Henderson ◽  
Mark A. Schembri ◽  
...  

ABSTRACT Uropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract infection, which in some patients can develop into life-threatening urosepsis. Serum resistance is a key virulence trait of strains that cause urosepsis. Recently, we identified a novel method of serum resistance in patients with Pseudomonas aeruginosa lung infections, where patients possessed antibodies that inhibited complement-mediated killing (instead of protecting against infection). These inhibitory antibodies were of the IgG2 subtype, specific to the O-antigen component of lipopolysaccharide (LPS) and coated the bacterial surface, preventing bacterial lysis by complement. As this mechanism could apply to any Gram-negative bacterial infection, we hypothesized that inhibitory antibodies may represent an uncharacterized mechanism of serum resistance in UPEC. To test this, 45 urosepsis patients with paired blood culture UPEC isolates were screened for serum titers of IgG2 specific for their cognate strain’s LPS. Eleven patients had sufficiently high titers of the antibody to inhibit serum-mediated killing of UPEC isolates by pooled healthy control sera. Depletion of IgG or removal of O-antigen restored sensitivity of the isolates to the cognate patient serum. Importantly, the isolates from these 11 patients were more sensitive to killing by serum than isolates from patients with no inhibitory antibodies. This suggests the presence of inhibitory antibodies may have allowed these strains to infect the bloodstream. The high prevalence of patients with inhibitory antibodies (24%) suggests that this phenomenon is an important mechanism of UPEC serum resistance. LPS-specific inhibitory antibodies have now been identified against three Gram-negative pathogens that cause disparate diseases. IMPORTANCE Despite improvements in the early detection and management of sepsis, morbidity and mortality are still high. Infections of the urinary tract are one of the most frequent sources of sepsis with Escherichia coli the main causative agent. Serum resistance is vital for bacteria to infect the bloodstream. Here we report a novel method of serum resistance found in patients with UPEC-mediated sepsis. Antibodies in sera usually protect against infection, but here we found that 24% of patients expressed “inhibitory antibodies” capable of preventing serum-mediated killing of their infecting isolate. Our data suggest that these antibodies would allow otherwise serum-sensitive UPEC strains to cause sepsis. The high prevalence of patients with inhibitory antibodies in this cohort suggests that this is a widespread mechanism of resistance to complement-mediated killing in urosepsis patients, invoking the potential for the application of new methods to prevent and treat sepsis.



2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Marlon H. Cardoso ◽  
Suzana M. Ribeiro ◽  
Diego O. Nolasco ◽  
César de la Fuente-Núñez ◽  
Mário R. Felício ◽  
...  

Abstract Due to the growing concern about antibiotic-resistant microbial infections, increasing support has been given to new drug discovery programs. A promising alternative to counter bacterial infections includes the antimicrobial peptides (AMPs), which have emerged as model molecules for rational design strategies. Here we focused on the study of Pa-MAP 1.9, a rationally designed AMP derived from the polar fish Pleuronectes americanus. Pa-MAP 1.9 was active against Gram-negative planktonic bacteria and biofilms, without being cytotoxic to mammalian cells. By using AFM, leakage assays, CD spectroscopy and in silico tools, we found that Pa-MAP 1.9 may be acting both on intracellular targets and on the bacterial surface, also being more efficient at interacting with anionic LUVs mimicking Gram-negative bacterial surface, where this peptide adopts α-helical conformations, than cholesterol-enriched LUVs mimicking mammalian cells. Thus, as bacteria present varied physiological features that favor antibiotic-resistance, Pa-MAP 1.9 could be a promising candidate in the development of tools against infections caused by pathogenic bacteria.



Author(s):  
G. E. Tyson ◽  
B. J. Stojanovic ◽  
R. Kuklinski ◽  
T. DiVittorio ◽  
M. Sullivan

Pierce's disease (PD) of grapevines is caused by a rod-shaped, gram-negative bacterium that is transmitted by xylem-feeding suctorial insects. Petioles from a grapevine (four-year old French-American hybrid, cultivar DeChaunac) with overt symptoms typical of PD were examined by conventional scanning and transmission electron microscopy in order to describe the external morphology of intraxylar bacterial aggregates and to verify the presence of features known from previous studies to be characteristic of PD bacteria. These features included the size and rod-shape of the bacterium (1.0-2.2 μm long, 0.39-0.53 μm wide), the ridged nature of the bacterial surface (Fig. 1), the membrane-like ultrastructure of the cell wall typical of gram-negative cells, and the xylem-limited occurrence within the host plant.



mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Elizabeth R. Aguilera ◽  
Y Nguyen ◽  
Jun Sasaki ◽  
Julie K. Pfeiffer

ABSTRACTSeveral viruses encounter various bacterial species within the host and in the environment. Despite these close encounters, the effects of bacteria on picornaviruses are not completely understood. Previous work determined that poliovirus (PV), an enteric virus, has enhanced virion stability when exposed to bacteria or bacterial surface polysaccharides such as lipopolysaccharide. Virion stabilization by bacteria may be important for interhost transmission, since a mutant PV with reduced bacterial binding had a fecal-oral transmission defect in mice. Therefore, we investigated whether bacteria broadly enhance stability of picornaviruses from three different genera:Enterovirus(PV and coxsackievirus B3 [CVB3]),Kobuvirus(Aichi virus), andCardiovirus(mengovirus). Furthermore, to delineate strain-specific effects, we examined two strains of CVB3 and a PV mutant with enhanced thermal stability. We determined that specific bacterial strains enhance thermal stability of PV and CVB3, while mengovirus and Aichi virus are stable at high temperatures in the absence of bacteria. Additionally, we determined that bacteria or lipopolysaccharide can stabilize PV, CVB3, Aichi virus, and mengovirus during exposure to bleach. These effects are likely mediated through direct interactions with bacteria, since viruses bound to bacteria in a pulldown assay. Overall, this work reveals shared and distinct effects of bacteria on a panel of picornaviruses.IMPORTANCERecent studies have shown that bacteria promote infection and stabilization of poliovirus particles, but the breadth of these effects on other members of thePicornaviridaefamily is unknown. Here, we compared the effects of bacteria on four distinct members of thePicornaviridaefamily. We found that bacteria reduced inactivation of all of the viruses during bleach treatment, but not all viral strains were stabilized by bacteria during heat treatment. Overall, our data provide insight into how bacteria play differential roles in picornavirus stability.



1992 ◽  
Vol 59 (3) ◽  
pp. 381-388 ◽  
Author(s):  
Beatriz Suárez ◽  
Carlos M. Ferreirós ◽  
Maria-Teresa Criado

SummaryPsychrotrophic bacteria isolated from raw milk were tested for their ability to adhere to steel, two types of rubber, and glass, materials employed in the construction of milking equipment. The adherence assays were carried out by exposure of the materials to radioactively labelled bacteria in both a buffering solution (Ringer's) and milk. The degree of adherence of Gram-positive bacteria was lower (P< 0·001) than that of Gram-negative bacteria. Glass was the material least prone to bacterial adherence (P< 0·001); there were no significant differences between the other three materials. Milk was found to inhibit adhesion significantly (P< 0·05), this inhibition being more evident with the most adherent bacteria. There was no statistically significant correlation between bacterial surface hydrophobicity and adherence. Our results suggest that intrinsic bacterial adherence cannot be considered a relevant factor in the contamination of milking equipment.



Sign in / Sign up

Export Citation Format

Share Document