The War between Bacteria and Bacteriophages

The rapid emergence and dissemination of multidrug-resistant (MDR) bacteria represents a worldwide crisis concerning that humankind is re-entering the ‘pre-antibiotics’ era. Before the discovery of antibiotics, bacteriophage therapy was widely enforced to combat bacterial infections. However, the discovery of penicillin in 1940 and other novel antibiotics replaced phage therapy, and they are being used as the first line of defence against pathogenic bacterial infections. Factors such as selective pressure resulted in bacteria becoming insensitive to one or multiple antibiotics, frequently leading to limited treatment options. This prompted a renewal of interest to the phage therapy that remains dubious due to its disadvantages such as host specificity and the development of bacterial resistance against phages. Evolution of bacterial genomes allowed bacteria to acquire vast mechanisms interfering with phage infection such as inhibition of phage adsorption, prevention of phage entry, superinfection exclusion, restriction-modification and abortive infection. Interestingly, phages have developed diverse counterstrategies to circumvent bacterial anti-phage mechanisms including digging for receptors, adapting to new receptors and masking and modifying restriction sites. Understanding the complex dynamics of bacteria-phage interaction is a preliminary step towards designing synthetic phages that can overcome limitations of phage therapy and potentially lead to defeating MDR bacteria

Characterisation of Phage Susceptibility Variation in Salmonellaenterica Serovar Typhimurium DT104 and DT104b

The surge in mortality and morbidity rates caused by multidrug-resistant (MDR) bacteria prompted a renewal of interest in bacteriophages (phages) as clinical therapeutics and natural biocontrol agents. Nevertheless, bacteria and phages are continually under the pressure of the evolutionary phage–host arms race for survival, which is mediated by co-evolving resistance mechanisms. In Anderson phage typing scheme of Salmonella Typhimurium, the epidemiologically related definitive phage types, DT 104 and DT 104b, display significantly different phage susceptibility profiles. This study aimed to characterise phage resistance mechanisms and genomic differences that may be responsible for the divergent phage reaction patterns in S. Typhimurium DT104 and DT104b using whole genome sequencing (WGS). The analysis of intact prophages, restriction–modification systems (RMS), plasmids and clustered regularly interspaced short palindromic repeats (CRISPRs), as well as CRISPR-associated proteins, revealed no unique genetic determinants that might explain the variation in phage susceptibility among the two phage types. Moreover, analysis of genes coding for potential phage receptors revealed no differences among DT104 and DT104b strains. However, the findings propose the need for experimental assessment of phage-specific receptors on the bacterial cell surface and analysis of bacterial transcriptome using RNA sequencing which will explain the differences in bacterial susceptibility to phages. Using Anderson phage typing scheme of Salmonella Typhimurium for the study of bacteria-phage interaction will help improving our understanding of host–phage interactions which will ultimately lead to the development of phage-based technologies, enabling effective infection control

Indigenous amino acids in primitive CR meteorites

CR meteorites are among the most primitive meteorites. In this paper, we report the first measurements of amino acids in Antarctic CR meteorites, two of which show the highest amino acid concentrations ever found in a chondrite. EET92042, GRA95229 and GRO95577 were analyzed for their amino acid content using high performance liquid chromatography with UV fluorescence detection (HPLC-FD) and gas chromatographymass spectrometry (GC-MS). Our data show that EET92042 and GRA95229 are the most amino acid-rich chondrites ever analyzed, with total amino acid concentrations ranging from 180 parts-per-million (ppm) to 249 ppm. GRO95577, however, is depleted in amino acids. The most abundant amino acids present in the EET92042 and GRA95229 meteorites are the alpha-amino acids glycine, isovaline, alpha-aminoisobutyric acid (alpha-AIB), and alanine, with delta13C values ranging from +31.6per mil to +50.5per mil. The carbon isotope results together with racemic enantiomeric ratios determined for most amino acids strongly indicate an extraterrestrial origin of these compounds. In addition, the relative abundances of alpha-AIB and beta-alanine in the Antarctic CR meteorites analyzed appear to correspond to the degree of aqueous alteration on their respective parent body.Comment: In press; To appear in the December 2007 issue of Meteoritics and Planetary Science, released March 200

The dynamics of the non-heme iron in bacterial reaction centers from Rhodobacter sphaeroides

AbstractWe investigate the dynamical properties of the non-heme iron (NHFe) in His-tagged photosynthetic bacterial reaction centers (RCs) isolated from Rhodobacter (Rb.) sphaeroides. Mössbauer spectroscopy and nuclear inelastic scattering of synchrotron radiation (NIS) were applied to monitor the arrangement and flexibility of the NHFe binding site. In His-tagged RCs, NHFe was stabilized only in a high spin ferrous state. Its hyperfine parameters (IS=1.06±0.01mm/s and QS=2.12±0.01mm/s), and Debye temperature (θD0~167K) are comparable to those detected for the high spin state of NHFe in non-His-tagged RCs. For the first time, pure vibrational modes characteristic of NHFe in a high spin ferrous state are revealed. The vibrational density of states (DOS) shows some maxima between 22 and 33meV, 33 and 42meV, and 53 and 60meV and a very sharp one at 44.5meV. In addition, we observe a large contribution of vibrational modes at low energies. This iron atom is directly connected to the protein matrix via all its ligands, and it is therefore extremely sensitive to the collective motions of the RC protein core. A comparison of the DOS spectra of His-tagged and non-His-tagged RCs from Rb. sphaeroides shows that in the latter case the spectrum was overlapped by the vibrations of the heme iron of residual cytochrome c2, and a low spin state of NHFe in addition to its high spin one. This enabled us to pin-point vibrations characteristic for the low spin state of NHFe

Community-acquired Klebsiella pneumoniae meningitis in an alcoholic patient with an infected pancreatic pseudocyst; a case report and review of literature

We report a case of a 49-year-old male with a history of chronic alcoholism and evidence of a pancreatic pseudocyst on CT scanning. He presented with a 3-days history of fever, loss of appetite and upper abdominal pain. Blood cultures grew Klebsiella pneumoniae and he improved clinically with a seven-day course of intravenous co-amoxiclav and metronidazole. Two weeks later he was readmitted to hospital with impaired consciousness and septic shock, and died three days later in intensive care. Post mortem examination revealed bacterial meningitis and an infected pancreatic pseudocyst. Klebsiella pneumoniae was isolated from the pancreas and meninges

Viral FLICE Inhibitory Protein of Rhesus Monkey Rhadinovirus Inhibits Apoptosis by Enhancing Autophagosome Formation

Rhesus monkey rhadinovirus (RRV) is a gamma-2 herpesvirus closely related to human herpesvirus 8 (HHV8). RRV encodes viral FLICE inhibitory protein (vFLIP), which has death effector domains. Little is known about RRV vFLIP. This study intended to examine its function in apoptosis. Here we found that RRV vFLIP inhibits apoptosis induced by tumor necrosis factor-α (TNF-α) and cycloheximide. In HeLa cells with vFLIP expression, the cleavage of poly [ADP-ribose] polymerase 1 (PARP-1) and activities of caspase 3, 7, and 9 were much lower than those in controls. Cell viability of HeLa cells with vFLIP expression was significantly higher than control cells after apoptosis induction. However, RRV vFLIP appears unable to induce NF-κB signaling when tested in NF-κB reporter assay. RRV vFLIP was able to enhance cell survival under starved conditions or apoptosis induction. At early time points after apoptosis induction, autophagosome formation was enhanced and LC3-II level was elevated in cells with vFLIP and, when autophagy was blocked with chemical inhibitors, these cells underwent apoptosis. Moreover, RRV latent infection of BJAB B-lymphoblastoid cells protects the cells against apoptosis by enhancing autophagy to maintain cell survival. Knockdown of vFLIP expression in the RRV-infected BJAB cells with siRNA abolished the protection against apoptosis. These results indicate that vFLIP protects cells against apoptosis by enhancing autophagosome formation to extend cell survival. The finding of vFLIP’s inhibition of apoptosis via the autophagy pathway provides insights of vFLIP in RRV pathogenesis

Coping strategies of women with postpartum depression symptoms in rural Ethiopia: a cross-sectional community study

Background: Most women with postpartum depression (PPD) in low- and middle-income countries remain undiagnosed and untreated, despite evidence for adverse effects on the woman and her child. The aim of this study was to identify the coping strategies used by women with PPD symptoms in rural Ethiopia to inform the development of socio-culturally appropriate interventions. Methods: A population-based, cross-sectional study was conducted in a predominantly rural district in southern Ethiopia. All women with live infants between one and 12 months post-partum (n = 3147) were screened for depression symptoms using the validated Patient Health Questionnaire, 9 item version (PHQ-9). Those scoring five or more, ‘high PPD symptoms’, (n = 385) were included in this study. The Brief Coping with Problems Experienced (COPE-28) scale was used to assess coping strategies. Construct validity of the brief COPE was evaluated using confirmatory factor analysis. Results: Confirmatory factor analysis of the brief COPE scale supported the previously hypothesized three dimensions of coping (problem-focused, emotion-focused, and dysfunctional). Emotion-focused coping was the most commonly employed coping strategy by women with PPD symptoms. Urban residence was associated positively with all three dimensions of coping. Women who had attended formal education and who attributed their symptoms to a physical cause were more likely to use both problem-focused and emotion-focused coping strategies. Women with better subjective wealth and those who perceived that their husband drank too much alcohol were more likely to use emotion-focused coping. Dysfunctional coping strategies were reported by women who had a poor relationship with their husbands. Conclusions: As in high-income countries, women with PPD symptoms were most likely to use emotion-focused and dysfunctional coping strategies. Poverty and the low level of awareness of depression as an illness may additionally impede problem-solving attempts to cope. Prospective studies are needed to understand the prognostic significance of coping styles in this setting and to inform psychosocial intervention development