Changing pattern of severe manifestations of Plasmodium falciparum and Plasmodium vivax malaria: A retrospective study from Bikaner, India.

BACKGROUND & OBJECTIVES: Previously there were reports from all over India about the changing spectrum of severe manifestations of Plasmodium falciparum malaria. Consequently, the present retrospective study was conducted to compare the severity of malaria caused by P. falciparum and P. vivax during 2007-08 and 2017-18. METHODS: The present study was conducted on the patients admitted with severe malaria in a classified malaria ward of a tertiary care hospital in Bikaner, Rajasthan (Northwest India) during 2007-08 and 2017-18. It included adult patients of both sexes belonging to all age groups. The diagnosis was done by peripheral blood film (PBF), rapid diagnostic test (RDT), and validated by polymerase chain reaction (PCR). All patients were treated with intravenous oral quinine. The specific individual malaria complications registered in 2007-08 and 2017-18 were treated by following the standard WHO protocol. RESULTS: In 2007-08, severe manifestations caused by P. falciparum were dominated by thrombocytopenia (25.98%) followed by jaundice (24.39%), multi-organ dysfunction (MODS) (16.66%), severe anemia (16.17%), cerebral malaria (5.39%), bleeding manifestation (3.92%) and shock (0.49%). While in the same year, P. vivax associated clinical spectrum of complications were observed to be dominated by thrombocytopenia (26.47%) followed by jaundice (25.00%), MODS (14.70%), severe anemia (5.88%), cerebral malaria (5.88%), renal failure (4.41%), bleeding manifestation (2.45%), shock (0.98%) and acute respiratory distress syndrome (ARDS) (0.49%). However, in 2017-18, the clinical spectrum of malaria complications caused by both species has changed. Relative to P. falciparum infections, P. vivax individual complications like thrombocytopenia (51.78%) (p<0.001) followed by jaundice (19.13%) (p<0.001) and severe anemia (4.22%) (p<0.05) were found to have increased significantly. INTERPRETATION & CONCLUSION: Over the last decade there is an apparent spatial and temporal shift in the clinical manifestations of severe malaria caused by the both Plasmodium species. As evident from the patient's data from 2007-08 and 2017-18, the severity is more inclined towards Plasmodium vivax than Plasmodium falciparum malaria. Moreover, individual P. falciparum-associated complications were decreased significantly in the Bikaner region of Rajasthan, India.

Adaptive laboratory evolution triggers pathogen-dependent broad-spectrum antimicrobial potency in Streptomyces.

BACKGROUND: In the present study, adaptive laboratory evolution was used to stimulate antibiotic production in a Streptomyces strain JB140 (wild-type) exhibiting very little antimicrobial activity against bacterial pathogens. The seven different competition experiments utilized three serial passages (3 cycles of adaptation-selection of 15 days each) in which Streptomyces strain (wild-type) was challenged repeatedly to one (bi-culture) or two (tri-culture) or three (quadri-culture) target pathogens. The study demonstrates a simple laboratory model to study the adaptive potential of evolved phenotypes and genotypes in Streptomyces to induce antibiotic production. RESULTS: Competition experiments resulted in the evolution of the wild-type Streptomyces strain JB140 into the seven unique mutant phenotypes that acquired the ability to constitutively exhibit increased antimicrobial activity against three bacterial pathogens Salmonella Typhi (NCIM 2051), Staphylococcus aureus (NCIM 2079), and Proteus vulgaris (NCIM 2027). The mutant phenotypes not only effectively inhibited the growth of the tested pathogens but were also observed to exhibit improved antimicrobial responses against one clinical multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC 1021) isolate. In contrast to the adaptively evolved mutants, only a weak antimicrobial activity was detected in the wild-type parental strain. To get molecular evidence of evolution, RAPD profiles of the wild-type Streptomyces and its evolved mutants were compared which revealed significant polymorphism among them. CONCLUSION: The competition-based adaptive laboratory evolution method can constitute a platform for evolutionary engineering to select improved phenotypes (mutants) with increased antibacterial profiles against targeted pathogens.

Draft Genome Sequence of Streptomyces sp. Strain DH-12, a Soilborne Isolate from the Thar Desert with Broad-Spectrum Antibacterial Activity.

Strain DH-12 exhibits broad-spectrum antibacterial activity toward Gram-positive and Gram-negative pathogens. The 7.6-Mb draft genome sequence gives insight into the complete secondary metabolite production capacity and reveals genes putatively responsible for its antibacterial activity, as well as genes which enable the survival of the organism in an extreme arid environment.

Regulation of gene expression: Cryptic β-glucoside (bgl) operon of Escherichia coli as a paradigm

Bacteria have evolved various mechanisms to extract utilizable substrates from available resources and consequently acquire fitness advantage over competitors. One of the strategies is the exploitation of cryptic cellular functions encoded by genetic systems that are silent under laboratory conditions, such as the bgl (β-glucoside) operon of E. coli. The bgl operon of Escherichia coli, involved in the uptake and utilization of aromatic β-glucosides salicin and arbutin, is maintained in a silent state in the wild type organism by the presence of structural elements in the regulatory region. This operon can be activated by mutations that disrupt these negative elements. The fact that the silent bgl operon is retained without accumulating deleterious mutations seems paradoxical from an evolutionary view point. Although this operon appears to be silent, specific physiological conditions might be able to regulate its expression and/or the operon might be carrying out function(s) apart from the utilization of aromatic β-glucosides. This is consistent with the observations that the activated operon confers a Growth Advantage in Stationary Phase (GASP) phenotype to Bgl+ cells and exerts its regulation on at least twelve downstream target genes.

Regulation of gene expression: cryptic ß-glucoside (bgl) operon of Escherichia coli as a paradigm.

Bacteria have evolved various mechanisms to extract utilizable substrates from available resources and consequently acquire fitness advantage over competitors. One of the strategies is the exploitation of cryptic cellular functions encoded by genetic systems that are silent under laboratory conditions, such as the bgl (ß-glucoside) operon of E. coli. The bgl operon of Escherichia coli, involved in the uptake and utilization of aromatic ß-glucosides salicin and arbutin, is maintained in a silent state in the wild type organism by the presence of structural elements in the regulatory region. This operon can be activated by mutations that disrupt these negative elements. The fact that the silent bgl operon is retained without accumulating deleterious mutations seems paradoxical from an evolutionary view point. Although this operon appears to be silent, specific physiological conditions might be able to regulate its expression and/or the operon might be carrying out function(s) apart from the utilization of aromatic ß-glucosides. This is consistent with the observations that the activated operon confers a Growth Advantage in Stationary Phase (GASP) phenotype to Bgl(+) cells and exerts its regulation on at least twelve downstream target genes.

The ß-glucoside (bgl) operon of Escherichia coli is involved in the regulation of oppA, encoding an oligopeptide transporter.

We report that the bgl operon of Escherichia coli, encoding the functions necessary for the uptake and metabolism of aryl-ß-glucosides, is involved in the regulation of oligopeptide transport during stationary phase. Global analysis of intracellular proteins from Bgl-positive (Bgl(+)) and Bgl-negative (Bgl(-)) strains revealed that the operon exerts regulation on at least 12 downstream target genes. Of these, oppA, which encodes an oligopeptide transporter, was confirmed to be upregulated in the Bgl(+) strain. Loss of oppA function results in a partial loss of the growth advantage in stationary-phase (GASP) phenotype of Bgl(+) cells. The regulatory effect of the bgl operon on oppA expression is indirect and is mediated via gcvA, the activator of the glycine cleavage system, and gcvB, which regulates oppA at the posttranscriptional level. We show that BglG destabilizes the gcvA mRNA in vivo, leading to reduced expression of gcvA in the stationary phase. Deletion of gcvA results in the downregulation of gcvB and upregulation of oppA and can partially rescue the loss of the GASP phenotype seen in ΔbglG strains. A possible mechanism by which oppA confers a competitive advantage to Bgl(+) cells relative to Bgl(-) cells is discussed.