Simkania Negevensis in Bronchoalveolar Lavage of Lung Transplant Recipients: A Possible Association with Acute Rejection

Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Transplantation (Impact Factor: 3.83). 01/2007; 83(2):138-43. DOI: 10.1097/
Source: PubMed


Simkania negevensis is a novel organism closely related to chlamydiae. The organism has been associated with community acquired pneumonia and acute exacerbation of chronic obstructive pulmonary disease. The prevalence and pathogenic potential of S. negevensis is not known in lung transplant recipients.
In this multicenter study comparative analysis of bronchoalveolar lavage (BAL) in lung transplants (Tx) and kidney Tx, immunocompromised and nasopharyngeal (NP) washes of immunocompetent patients was done. The BAL specimens were tested by nested polymerase chain reaction (PCR) for C. pneumoniae and S. negevensis. Selected S. negevensis positive PCR cases were confirmed by culture.
In the initial 41 BAL samples S. negevensis was detected in 97.5% (40/41) of lung transplant recipients as compared to 14.1% (1/7) in other organ transplant recipients (P<0.0001). In the sequential samples of 19 lung transplant recipients, 59% (24/41) had concomitant positive PCR and rejection as compared to 30% (3/10) who had negative PCR but had rejection (P=0.16). S. negevensis infection had hazard ratio of 3.29 (95% CI: 0.73-14.76; P=0.11) for developing acute rejection.
S. negevensis is highly prevalent in liver Tx recipients and may be associated with acute rejection.

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    • "Seropositivity for Simkania has been shown to be highly prevalent among children with bronchiolitis and adults with pneumonia (Friedman et al., 1999; Kahane et al., 1999; Lieberman et al., 2002). Simkania has also been associated with chronic obstructive pulmonary disease and transplant rejection (Lieberman et al., 2002; Husain et al., 2007). "
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    ABSTRACT: Most intracellular bacterial pathogens reside within membrane-surrounded host derived vacuoles. Few of these bacteria exploit membranes from the host's endoplasmic reticulum (ER) to form a replicative vacuole. Here, we describe the formation of ER-vacuole contact sites as part of the replicative niche of the chlamydial organism Simkania negevensis. Formation of ER-vacuole contact sites is evolutionary conserved in the distantly related protozoan host Acanthamoeba castellanii. Simkania growth is accompanied by mitochondria associating with the Simkania containing vacuole (SCV). Super-resolution microscopy as well as 3D-reconstruction from electron micrographs of serial ultra-thin sections revealed a single vacuolar system forming extensive ER-SCV contact sites on the Simkania vacuolar surface. Simkania infection induced an ER-stress response, which was later down-regulated. Induction of ER-stress with Thapsigargin or Tunicamycin was strongly inhibited in cells infected with Simkania. Inhibition of ER-stress was required for inclusion formation and efficient growth, demonstrating a role of ER-stress in the control of Simkania infection. Thus, Simkania forms extensive ER-SCV contact sites in host species evolutionary as diverse as human and amoeba. Moreover, Simkania is the first bacterial pathogen described to interfere with ER-stress induced signaling to promote infection.
    Cellular Microbiology 02/2014; 16(8). DOI:10.1111/cmi.12278 · 4.92 Impact Factor
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    • "They are obligate intracellular gram-negative bacteria which replicate within endocytic vacuoles of eukaryotic cells i.e. amoebae, human epithelial cells and macrophages [3]. Simkania has been reported as an emerging pathogen associated with several types of respiratory tract infection such as bronchiolitis in infants [4], [5], [6], [7], community acquired pneumonia [8], [9], [10], chronic obstructive pulmonary disease in adults [11] and acute rejection in lung transplant recipients [12]. Moreover, seroprevalence rates in adults between 46–80% suggest a broad distribution of the organism in human populations [13]. "
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    ABSTRACT: Control of host cell death is of paramount importance for the survival and replication of obligate intracellular bacteria. Among these, human pathogenic Chlamydia induces the inhibition of apoptosis in a variety of different host cells by directly interfering with cell death signaling. However, the evolutionary conservation of cell death regulation has not been investigated in the order Chlamydiales, which also includes Chlamydia-like organisms with a broader host spectrum. Here, we investigated the apoptotic response of human cells infected with the Chlamydia-like organism Simkania negevensis (Sn). Simkania infected cells exhibited strong resistance to apoptosis induced by intrinsic stress or by the activation of cell death receptors. Apoptotic signaling was blocked upstream of mitochondria since Bax translocation, Bax and Bak oligomerisation and cytochrome c release were absent in these cells. Infected cells turned on pro-survival pathways like cellular Inhibitor of Apoptosis Protein 2 (cIAP-2) and the Akt/PI3K pathway. Blocking any of these inhibitory pathways sensitized infected host cell towards apoptosis induction, demonstrating their role in infection-induced apoptosis resistance. Our data support the hypothesis of evolutionary conserved signaling pathways to apoptosis resistance as common denominators in the order Chlamydiales.
    PLoS ONE 07/2011; 6(7):e22528. DOI:10.1371/journal.pone.0022528 · 3.23 Impact Factor
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    • "Coinfections with other pathogens have been described, such as respiratory syncytial virus in children and influenza virus and other bacterial species in adults [7] [8] [11]. A possible association between S. negevensis and acute rejection in lung transplant recipients has been suggested [12]. S. negevensis DNA has also been amplified from an aortic aneurysm [13] [14]. "
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    ABSTRACT: The in vitro activity of six cathelicidin peptides against the reference strain Z of Simkania negevensis was investigated. Five peptides-PG-1, Bac7, SMAP-29, BMAP-27, and BMAP-28-proved to be active at very low concentrations (1 to 0.1 μg/mL), while LL-37 cathelicidin was ineffective even at a concentration of 100 μg/mL. In comparison to chlamydiae, S. negevensis proved to be more susceptible to the antimicrobial peptides tested.
    International Journal of Peptides 04/2011; 2011:708710. DOI:10.1155/2011/708710
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