Excess haemoglobin digestion by malaria parasites: a strategy to prevent premature host cell lysis

2004 ◽  
Vol 32 (3) ◽  
pp. 353-359 ◽  
Author(s):  
Virgilio L Lew ◽  
Lynn Macdonald ◽  
Hagai Ginsburg ◽  
Miriam Krugliak ◽  
Teresa Tiffert
2006 ◽  
Vol 59 (3) ◽  
pp. 779-794 ◽  
Author(s):  
Tobias Spielmann ◽  
Donald L. Gardiner ◽  
Hans-Peter Beck ◽  
Katharine R. Trenholme ◽  
David J. Kemp

2021 ◽  
Author(s):  
Jothi Ranjani ◽  
Ramamoorthy Sivakumar ◽  
Paramasamy Gunasekaran ◽  
Jeyaprakash Rajendhran

AbstractPseudomonas aeruginosais the major infectious agent among Gram-negative bacteria which causes both acute and chronic infections without any tissue specificity. Infections due toP. aeruginosaare hard to treat, as it entails various strategies like virulence factors synthesis, drug efflux systems & resistance and protein secretion systems during pathogenesis. Despite extensive research inPseudomonaspathogenesis, novel drug targets and potential therapeutic strategies are inevitable. In this study, we investigated the genetic requirements ofP.aeruginosaPAO1 for rat cardiomyocyte (H9C2) infection by insertion sequencing (INSeq). A mutant library comprising ~70,000 mutants of PAO1 was generated and the differentiated form of H9C2 cells (d-H9C2) was infected with the library. The infected d-H9C2 cells were maintained with antibiotic-protection and without any antibiotics in the growth media for 24 h. Subsequently, DNA library for INSeq was prepared, sequenced and fitness analysis was performed. A-One hundred and thirteen mutants were negatively selected in the infection condition with antibiotic-protection, whereas 143 mutants were negatively selected in antibiotic-free condition. Surprisingly, a higher number of mutants showed enriched fitness than the mutants of reduced fitness during the infection. We demonstrated that the genes associated with flagella and T3SS are important for adhesion and invasion of cardiomyocytes, while pili and proteases are conditionally essential during host cell lysis.Take away✓Fitness ofP.aeruginosamutants were analyzed during cardiomyocyte infection✓Genes involve amino acid transport & metabolism and signal transduction are important during intracellular lifestyle✓OMVs play a crucial role during infection and pathogenesis✓Flagella and T3SS are conditionally essential for adhesion and invasion, whereas pili and proteases are conditionally essential during host cell lysis


1998 ◽  
Vol 180 (8) ◽  
pp. 2110-2117 ◽  
Author(s):  
Susanne Krogh ◽  
Steen T. Jørgensen ◽  
Kevin M. Devine

ABSTRACT Four genes identified within the late operon of PBSX show characteristics expected of a host cell lysis system; they arexepA, encoding an exported protein; xhlA, encoding a putative membrane-associated protein; xhlB, encoding a putative holin; and xlyA, encoding a putative endolysin. In this work, we have assessed the contribution of each gene to host cell lysis by expressing the four genes in different combinations under the control of their natural promoter located on the chromosome of Bacillus subtilis 168. The results show thatxepA is unlikely to be involved in host cell lysis. Expression of both xhlA and xhlB is necessary to effect host cell lysis of B. subtilis. Expression ofxhlB (encoding the putative holin) together withxlyA (encoding the endolysin) cannot effect cell lysis, indicating that the PBSX lysis system differs from those identified in the phages of gram-negative bacteria. Since host cell lysis can be achieved when xlyA is inactivated, it is probable that PBSX encodes a second endolysin activity which also uses XhlA and XhlB for export from the cell. The chromosome-based expression system developed in this study to investigate the functions of the PBSX lysis genes should be a valuable tool for the analysis of other host cell lysis systems and for expression and functional analysis of other lethal gene products in gram-positive bacteria.


2019 ◽  
Vol 35 (5) ◽  
pp. 333-335 ◽  
Author(s):  
Brendan Elsworth ◽  
Caroline D. Keroack ◽  
Manoj T. Duraisingh

Virology ◽  
1978 ◽  
Vol 89 (1) ◽  
pp. 327-329 ◽  
Author(s):  
Jun-Ichi Miyazaki ◽  
Yeikou Ryo ◽  
Hisao Fujisawa ◽  
Teiichi Minagawa
Keyword(s):  

2017 ◽  
Vol 47 (2-3) ◽  
pp. 119-127 ◽  
Author(s):  
Paul R. Gilson ◽  
Scott A. Chisholm ◽  
Brendan S. Crabb ◽  
Tania F. de Koning-Ward

Virology ◽  
1967 ◽  
Vol 32 (4) ◽  
pp. 553-569 ◽  
Author(s):  
A.W. Harris ◽  
D.W.A. Mount ◽  
C.R. Fuerst ◽  
L. Siminovitch

2021 ◽  
Author(s):  
Jan Stephan Wichers ◽  
Carolina van Gelder ◽  
Gwendolin Fuchs ◽  
Julia Mareike Ruge ◽  
Emma Pietsch ◽  
...  

ABSTRACTDuring the symptomatic human blood phase, malaria parasites replicate within red blood cells. Parasite proliferation relies on the uptake of nutrients, such as amino acids, from the host cell and the blood plasma, requiring transport across multiple membranes. Amino acids are delivered to the parasite through the parasite surrounding vacuolar compartment by specialized nutrient-permeable channels of the erythrocyte membrane and the parasitophorous vacuole membrane (PVM). However, further transport of amino acid across the parasite plasma membrane (PPM) is currently not well characterized. In this study, we focused on a family of Apicomplexan amino acid transporters (ApiATs) that comprises five members in Plasmodium falciparum. First, we localized four of the PfApiATs at the PPM using endogenous GFP-tagging. Next, we applied reverse genetic approaches to probe into their essentiality during asexual replication and gametocytogenesis. Upon inducible knockdown and targeted gene disruption a reduced asexual parasite proliferation was detected for PfApiAT2 and PfApiAT4. Functional inactivation of individual PfApiATs targeted in this study had no effect on gametocyte development. Our data suggest that individual PfApiATs are partially redundant during asexual in vitro proliferation and fully redundant during gametocytogenesis of P. falciparum parasites.IMPORTANCEMalaria parasites live and multiply inside cells. To facilitate their extremely fast intracellular proliferation they hijack and transform their host cells. This also requires the active uptake of nutrients, such as amino acids, from the host cell and the surrounding environment through various membranes that are the consequence of the parasite’s intracellular lifestyle. In this manuscript we focus on a family of putative amino acid transporters termed ApiAT. We show expression and localization of four transporters in the parasite plasma membrane of Plasmodium falciparum-infected erythrocytes that represent one interface of the pathogen to its host cell. We probed into the impact of functional inactivation of individual transporters on parasite growth in asexual and sexual blood stages of P. falciparum and reveal that only two of them show a modest but significant reduction in parasite proliferation but no impact on gametocytogenesis pointing towards redundancy within this transporter family.


1993 ◽  
Vol 175 (12) ◽  
pp. 3909-3912 ◽  
Author(s):  
W D Roof ◽  
R Young
Keyword(s):  

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