scholarly journals Small proline-rich proteins (SPRRs) are epidermally produced antimicrobial proteins that defend the cutaneous barrier by direct bacterial membrane disruption

2021 ◽  
Author(s):  
Chenlu Zhang ◽  
Zehan Hu ◽  
Abdul G Lone ◽  
Methinee Artami ◽  
Marshall Edwards ◽  
...  

Human skin functions as a physical barrier, preventing the entry of foreign pathogens while also accommodating a myriad of commensal microorganisms. A key contributor to the skin landscape is the sebaceous gland. Mice devoid of sebocytes are prone to skin infection, yet our understanding of how sebocytes function in host defense is incomplete. Here we show that the small proline-rich proteins, SPRR1 and SPRR2 are bactericidal in skin. SPRR1B and SPPR2A were induced in human sebocytes by exposure to the bacterial cell wall component lipopolysaccharide (LPS). Further, LPS injected into mouse skin triggered the expression of the mouse SPRR orthologous genes, Sprr1a and Sprr2a, through stimulation of MYD88. Both mouse and human SPRR proteins displayed potent bactericidal activity against MRSA (methicillin-resistant Staphylococcus aureus), Pseudomonas aeruginosa and skin commensals. Thus, Sprr1a-/-;Sprr2a-/- mice are more susceptible to MRSA and Pseudomonas aeruginosa skin infection. Lastly, mechanistic studies demonstrate that SPRR proteins exert their bactericidal activity through binding and disruption of the bacterial membrane. Taken together, these findings provide insight into the regulation and antimicrobial function of SPRR proteins in skin and how the skin defends the host against systemic infection.

2008 ◽  
Vol 52 (10) ◽  
pp. 3694-3700 ◽  
Author(s):  
Bartolomé Moya ◽  
Carlos Juan ◽  
Sebastián Albertí ◽  
José L. Pérez ◽  
Antonio Oliver

ABSTRACT The inactivation of ampD in Pseudomonas aeruginosa leads to a partially derepressed phenotype, characterized by a moderately high level basal ampC expression that is still further inducible, due to the presence of two additional ampD genes in this species (ampDh2 and ampDh3). The sequential inactivation of the three ampD genes was shown to lead to a stepwise upregulation of ampC expression, reaching full derepression in the triple mutant. To gain insight into the biological role of P. aeruginosa AmpD multiplicity, we determined the effects of the inactivation of the ampD genes on fitness and virulence. We show that, in contrast to what was previously documented for Salmonella spp., the inactivation of ampD in P. aeruginosa does not affect fitness or virulence in a mouse model of systemic infection. This lack of effect was demonstrated to be dependent on the presence of the additional ampD genes (ampDh2 and ampDh3), since the double and the triple ampD mutants completely lost their biological competitiveness and virulence; full ampC derepression and disruption of the AmpD peptidoglycan recycling system itself are both found to cause a major biological cost. Furthermore, among the ampD genes, ampDh3 is found to be the most relevant for virulence in P. aeruginosa. Therefore, as a consequence of the presence of additional ampD genes, partial ampC derepression mediated by ampD inactivation confers a biologically efficient resistance mechanism on P. aeruginosa.


Vaccine ◽  
2021 ◽  
Author(s):  
Saori Ito ◽  
Jutaro Nakamura ◽  
Michiko Fukuta ◽  
Takehiro Ura ◽  
Takeshi Teshigawara ◽  
...  

2015 ◽  
Vol 14 ◽  
pp. S4
Author(s):  
M. Kolpen ◽  
C.F. Appeldorff ◽  
S. Brandt ◽  
N. Mousavi ◽  
K.N. Kragh ◽  
...  

2003 ◽  
Vol 77 (20) ◽  
pp. 11274-11278 ◽  
Author(s):  
B. W. A. van der Strate ◽  
J. L. Hillebrands ◽  
S. S. Lycklama à Nijeholt ◽  
L. Beljaars ◽  
C. A. Bruggeman ◽  
...  

ABSTRACT The role of leukocytes in the in vivo dissemination of cytomegalovirus was studied in this experiment. Rat cytomegalovirus (RCMV) could be transferred to rat granulocytes and monocytes by cocultivation with RCMV-infected fibroblasts in vitro. Intravenous injection of purified infected granulocytes or monocytes resulted in a systemic infection in rats, indicating that our model is a powerful tool to gain further insight into CMV dissemination and the development of new antivirals.


2014 ◽  
Vol 58 (9) ◽  
pp. 5297-5305 ◽  
Author(s):  
Tiffany R. Keepers ◽  
Marcela Gomez ◽  
Chris Celeri ◽  
Wright W. Nichols ◽  
Kevin M. Krause

ABSTRACTAvibactam, a non-β-lactam β-lactamase inhibitor with activity against extended-spectrum β-lactamases (ESBLs), KPC, AmpC, and some OXA enzymes, extends the antibacterial activity of ceftazidime against most ceftazidime-resistant organisms producing these enzymes. In this study, the bactericidal activity of ceftazidime-avibactam against 18Pseudomonas aeruginosaisolates and 15Enterobacteriaceaeisolates, including wild-type isolates and ESBL, KPC, and/or AmpC producers, was evaluated. Ceftazidime-avibactam MICs (0.016 to 32 μg/ml) were lower than those for ceftazidime alone (0.06 to ≥256 μg/ml) against all isolates except for 2P. aeruginosaisolates (1blaVIM-positive isolate and 1blaOXA-23-positive isolate). The minimum bactericidal concentration/MIC ratios of ceftazidime-avibactam were ≤4 for all isolates, indicating bactericidal activity. Human serum and human serum albumin had a minimal effect on ceftazidime-avibactam MICs. Ceftazidime-avibactam time-kill kinetics were evaluated at low MIC multiples and showed time-dependent reductions in the number of CFU/ml from 0 to 6 h for all strains tested. A ≥3-log10decrease in the number of CFU/ml was observed at 6 h for allEnterobacteriaceae, and a 2-log10reduction in the number of CFU/ml was observed at 6 h for 3 of the 6P. aeruginosaisolates. Regrowth was noted at 24 h for some of the isolates tested in time-kill assays. These data demonstrate the potent bactericidal activity of ceftazidime-avibactam and support the continued clinical development of ceftazidime-avibactam as a new treatment option for infections caused byEnterobacteriaceaeandP. aeruginosa, including isolates resistant to ceftazidime by mechanisms dependent on avibactam-sensitive β-lactamases.


2012 ◽  
Vol 17 (1) ◽  
pp. 72
Author(s):  
Janeth Arias-Palacios ◽  
Libardo Hernandez-Esquivel ◽  
Juan Carlos Marín-Díaz ◽  
Natalia Navarro-Peña ◽  
Natalia Santos-Arévalo

<strong>Objective</strong>. Evaluate the dilution-neutralization method proposed in the Colombian Technical Norm 5473/07, by using a gel, alcoholbased disinfectant. <strong>Materials and methods</strong>. This study was done using Pseudomonas aeruginosa ATCC 15442, Staphylococcus aureus ATCC 6538, and Enterococcus hirae ATCC 10541 as the assay microorganisms. The study was carried out at 20±1°C as obligatory temperature and additionally at 36±1°C. Four contact times between microorganisms and the disinfectant were evaluated (0, 2, 5 and 10 minutes). The assay was done both under clean conditions (0.3 g/L of bovine serum albumin), and unclean conditions (3 g/L of bovine serum albumin and 3g/L of sheep erythrocytes). <strong>Results</strong>. The implementation of this method produced precise results in all of the six<br />repetitions used during the assay. The obtained results demonstrated a logarithmic reduction higher than five, demonstrating the bactericidal activity exerted by the disinfectant on the control microorganisms. The established experimental conditions and methodology did not affect negatively the growth of any of the strains of microorganisms. Similarly, the neutralizing used did not inhibit the development of the microorganisms of the assay.<strong> Conclusions</strong>. The method was verified by means of the fulfillment of the limits set by the rule. Our results suggest that the method evaluated by means of the implementation of the protocol established in the Colombian Technical Norm 5473/07, allows evaluating the effectiveness of a disinfectant under selected and controlled experimental conditions.<br /><br /><strong>Key words</strong>: disinfection, clean conditions, unclean conditions, dilution-neutralization method, logarithmic reduction.


2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Mette Kolpen ◽  
Christian J. Lerche ◽  
Kasper N. Kragh ◽  
Thomas Sams ◽  
Klaus Koren ◽  
...  

ABSTRACT Chronic Pseudomonas aeruginosa lung infection is characterized by the presence of endobronchial antibiotic-tolerant biofilm, which is subject to strong oxygen (O2) depletion due to the activity of surrounding polymorphonuclear leukocytes. The exact mechanisms affecting the antibiotic susceptibility of biofilms remain unclear, but accumulating evidence suggests that the efficacy of several bactericidal antibiotics is enhanced by stimulation of aerobic respiration of pathogens, while lack of O2 increases their tolerance. In fact, the bactericidal effect of several antibiotics depends on active aerobic metabolism activity and the endogenous formation of reactive O2 radicals (ROS). In this study, we aimed to apply hyperbaric oxygen treatment (HBOT) to sensitize anoxic P. aeruginosa agarose biofilms established to mimic situations with intense O2 consumption by the host response in the cystic fibrosis (CF) lung. Application of HBOT resulted in enhanced bactericidal activity of ciprofloxacin at clinically relevant durations and was accompanied by indications of restored aerobic respiration, involvement of endogenous lethal oxidative stress, and increased bacterial growth. The findings highlight that oxygenation by HBOT improves the bactericidal activity of ciprofloxacin on P. aeruginosa biofilm and suggest that bacterial biofilms are sensitized to antibiotics by supplying hyperbaric O2.


1962 ◽  
Vol 8 (4) ◽  
pp. 491-499 ◽  
Author(s):  
June M. Stephens

The blood of normal wax moth larvae is not bactericidal for Pseudomonas aeruginosa. The blood becomes moderately bactericidal when larvae are actively immunized against P. aeruginosa. This activity was measured by a modification of Nagington's technique for the estimation of typhoid antibody. Bactericidal activity appears to be the only measurable type of antibody response against P. aeruginosa. Cell-free blood was as active as whole blood; 0.02 ml of immune serum kills about 1000 organisms. The blood of normal wax moth larvae is bactericidal for Shigella dysenteriae but the blood of insects immunized against either this organism or P. aeruginosa shows no increase in activity against S. dysenteriae. A number of non-specific agents, both protein and non-protein, did not stimulate bactericidal activity in serum after their injection into normal larvae. Immune sera prepared against some strains of P. aeruginosa were not active against other strains. Storage at 37 °C or absorption with zymosan both result in blackening of immune blood and loss of bactericidal activity. Bactericidal activity is evident only during the immune state of the insect, i.e. from about 18 hours until the third day after vaccination; it develops at the same time that inhibition of melanization was observed in the blood from vaccinated larvae.


1986 ◽  
Vol 60 (12) ◽  
pp. 1324-1333
Author(s):  
Akiyoshi TSUJI ◽  
Yumiko MUTO ◽  
Yasuko KANEKO ◽  
Sachiko GOTO

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