scholarly journals Acinetobacter baumannii: An Ancient Commensal with Weapons of a Pathogen

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 387
Author(s):  
Meysam Sarshar ◽  
Payam Behzadi ◽  
Daniela Scribano ◽  
Anna Teresa Palamara ◽  
Cecilia Ambrosi
Keyword(s):  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Current Data ◽  
Comparative Genomic ◽  
Host Immune System ◽  
Host Pathogen Interactions ◽  
In Vivo Models ◽  
Host Pathogen

Acinetobacter baumannii is regarded as a life-threatening pathogen associated with community-acquired and nosocomial infections, mainly pneumonia. The rise in the number of A. baumannii antibiotic-resistant strains reduces effective therapies and increases mortality. Bacterial comparative genomic studies have unraveled the innate and acquired virulence factors of A. baumannii. These virulence factors are involved in antibiotic resistance, environmental persistence, host-pathogen interactions, and immune evasion. Studies on host–pathogen interactions revealed that A. baumannii evolved different mechanisms to adhere to in order to invade host respiratory cells as well as evade the host immune system. In this review, we discuss current data on A. baumannii genetic features and virulence factors. An emphasis is given to the players in host–pathogen interaction in the respiratory tract. In addition, we report recent investigations into host defense systems using in vitro and in vivo models, providing new insights into the innate immune response to A. baumannii infections. Increasing our knowledge of A. baumannii pathogenesis may help the development of novel therapeutic strategies based on anti-adhesive, anti-virulence, and anti-cell to cell signaling pathways drugs.

scholarly journals Gene expression profiling in human neutrophils after infection with Acinetobacter baumannii in vitro

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242674
Author(s):  
María Lázaro-Díez ◽  
Itziar Chapartegui-González ◽  
Borja Suberbiola ◽  
J. Gonzalo Ocejo-Vinyals ◽  
Marcos López-Hoyos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acinetobacter Baumannii ◽  
Protein Quantification ◽  
Effector Proteins ◽  
Human Neutrophils ◽  
Host Pathogen Interactions ◽  
Proinflammatory Response ◽  
Host Pathogen ◽  
Key Aspects

Acinetobacter baumannii is a Gram negative nosocomial pathogen that has acquired increasing worldwide notoriety due to its high antibiotic resistance range and mortality rates in hospitalized patients. Therefore, it is necessary to better understand key aspects of A. baumannii pathogenesis such as host-pathogen interactions. In this report, we analyzed both gene expression and cytokine production by human neutrophils infected with A. baumannii. Our assays reveal a proinflammatory response of neutrophils after A. baumannii infection, since intracellular transcription of effector proteins such as COX-2, transcription factors, and proinflammatory cytokines resulted significantly upregulated in neutrophils infected by A. baumannii, compared with unstimulated human neutrophils. Translation and release of CXCL-8, IL-1β and TNF-α by neutrophils was confirmed by protein quantification in culture supernatants. Results obtained in this report reinforce the importance of human neutrophils in controlling A. baumannii infections but also emphasize the proinflammatory nature of these host-pathogen interactions as a target for future immunomodulatory therapies.

scholarly journals A bilayer tissue culture model of the bovine alveolus

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 357
Author(s):  
Diane Lee ◽  
Mark Chambers
Keyword(s):  
Epithelial Cells ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Host Pathogen Interactions ◽  
Alveolar Type Ii Cells ◽  
Permeable Membrane ◽  
Host Pathogen

The epithelial lining of the lung is often the first point of interaction between the host and inhaled pathogens, allergens and medications. Epithelial cells are therefore the main focus of studies which aim to shed light on host-pathogen interactions, to dissect the mechanisms of local host immunity and study toxicology. If these studies are not to be conducted exclusively in vivo, it is imperative that in vitro models are developed with a high in vitro-in vivo correlation. We describe here a co-culture bilayer model of the bovine alveolus, designed to overcome some of the limitations encountered with mono-culture and live animal models. Our system includes bovine pulmonary arterial endothelial cells (BPAECs) seeded onto a permeable membrane in 24 well Transwell format. The BPAECs are overlaid with immortalised bovine alveolar type II epithelial cells and the bilayer cultured at air-liquid interface for 14 days before use; in our case to study host-mycobacterial interactions. Characterisation of novel cell lines and the bilayer model have provided compelling evidence that immortalised bovine alveolar type II cells are an authentic substitute for primary alveolar type II cells and their culture as a bilayer in conjunction with BPAECs provides a physiologically relevant in vitro model of the bovine alveolus.   The bilayer model may be used to study dynamic intracellular and extracellular host-pathogen interactions, using proteomics, genomics, live cell imaging, in-cell ELISA and confocal microscopy. The model presented in this article enables other researchers to establish an in vitro model of the bovine alveolus that is easy to set up, malleable and serves as a comparable alternative to in vivo models, whilst allowing study of early host-pathogen interactions, currently not feasible in vivo. The model therefore achieves one of the 3Rs objectives in that it replaces the use of animals in research of bovine respiratory diseases.

scholarly journals Clinical Candida albicans Vaginal Isolates and a Laboratory Strain Show Divergent Behaviors during Macrophage Interactions

mSphere ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Franziska Gerwien ◽  
Christine Dunker ◽  
Philipp Brandt ◽  
Enrico Garbe ◽  
Ilse D. Jacobsen ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Fungal Infections ◽  
Laboratory Strain ◽  
Infection Process ◽  
Vulvovaginal Candidiasis ◽  
Host Immune System ◽  
Host Pathogen Interactions ◽  
Content Type ◽  
Host Pathogen

ABSTRACT Typically, established lab strains are widely used to study host-pathogen interactions. However, to better reflect the infection process, the experimental use of clinical isolates has come more into focus. Here, we analyzed the interaction of multiple vaginal isolates of the opportunistic fungal pathogen Candida albicans, the most common cause of vulvovaginal candidiasis in women, with key players of the host immune system: macrophages. We tested several strains isolated from asymptomatic or symptomatic women with acute and recurrent infections. While all clinical strains showed a response similar to the commonly used lab strain SC5314 in various in vitro assays, they displayed remarkable differences during interaction with macrophages. This coincided with significantly reduced β-glucan exposure on the cell surface, which appeared to be a shared property among the tested vaginal strains for yeast extract/peptone/dextrose-grown cells, which is partly lost when the isolates faced vaginal niche-like nutrient conditions. However, macrophage damage, survival of phagocytosis, and filamentation capacities were highly strain-specific. These results highlight the high heterogeneity of C. albicans strains in host-pathogen interactions, which have to be taken into account to bridge the gap between laboratory-gained data and disease-related outcomes in an actual patient. IMPORTANCE Vulvovaginal candidiasis is one of the most common fungal infections in humans with Candida albicans as the major causative agent. This study is the first to compare clinical vaginal isolates of defined patient groups in their interaction with macrophages, highlighting the vastly different outcomes in comparison to a laboratory strain using commonly applied virulence-determining assays.

In Vitro and in Vivo Models for Pathogenic Neisseria gonorrhoeae Infections

2021 ◽  
pp. 111-143
Author(s):  
Karthikeyan Ramalingam ◽  
Sucharithra Ganesh
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Sexually Transmitted Diseases ◽  
Virulence Factors ◽  
Public Awareness ◽  
In Vivo Models ◽  
Sexually Transmitted ◽  
General Aspects ◽  
General Community

The prevalence of gonorrhea has not discontinued in several countries and still remains as one of the top sexually transmitted diseases (STD) and it's caused by Neisseria gonorrhoeae. This bacterium gains entry into the human host via receptors, and by the usage of several virulence factors, it manages to spread through the cells and leads to severe complications. The study of these bacteria in various in vitro and in vivo models have paved the way for gaining insights on various aspects of bacterial infection, such as the study of pathogenesis of the organism in the host. It also drove the development of more appropriate drugs for the treatment of the gonorrhea illness caused by this ‘superbug'. This chapter focuses on providing a concise overview on the general aspects of N. gonorrhoeaeas an update and the in vitro and in vivo models used for understanding this bacterium over the years. Despite gonorrhea not being a rare STD, it is still a big challenge for researchers, healthcare professionals, and communicators with public awareness to communicate effectively with the general community.

scholarly journals Illuminating Macrophage Contributions to Host-Pathogen Interactions In Vivo: the Power of Zebrafish

2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Emily E. Rosowski
Keyword(s):  
Cell Culture ◽  
Innate Immunity ◽  
Imaging Techniques ◽  
Innate Immune ◽  
Host Pathogen Interactions ◽  
Culture Studies ◽  
Larval Zebrafish ◽  
Host Pathogen

ABSTRACT Macrophages are a key cell type in innate immunity. Years of in vitro cell culture studies have unraveled myriad macrophage pathways that combat pathogens and demonstrated how pathogen effectors subvert these mechanisms. However, in vitro cell culture studies may not accurately reflect how macrophages fit into the context of an innate immune response in whole animals with multiple cell types and tissues. Larval zebrafish have emerged as an intermediate model of innate immunity and host-pathogen interactions to bridge the gap between cell culture studies and mammalian models. These organisms possess an innate immune system largely conserved with that of humans and allow state-of-the-art genetic and imaging techniques, all in the context of an intact organism. Using larval zebrafish, researchers are elucidating the function of macrophages in response to many different infections, including both bacterial and fungal pathogens. The goal of this review is to highlight studies in zebrafish that utilized live-imaging techniques to analyze macrophage activities in response to pathogens. Recent studies have explored the roles of specific pathways and mechanisms in macrophage killing ability, explored how pathogens subvert these responses, identified subsets of macrophages with differential microbicidal activities, and implicated macrophages as an intracellular niche for pathogen survival and trafficking. Research using this model continues to advance our understanding of how macrophages, and specific pathways inside these cells, fit into complex multicellular innate immune responses in vivo, providing important information on how pathogens evade these pathways and how we can exploit them for development of treatments against microbial infections.

scholarly journals Insights from the Genome Sequence of Mycobacterium lepraemurium: Massive Gene Decay and Reductive Evolution

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Andrej Benjak ◽  
Tanvi P. Honap ◽  
Charlotte Avanzi ◽  
Enrique Becerril-Villanueva ◽  
Iris Estrada-García ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Pathogenic Species ◽  
Host Pathogen Interactions ◽  
Minimal Set ◽  
Free Living ◽  
Genetic Studies ◽  
Gene Set ◽  
Host Pathogen ◽  
Mycobacterium Lepraemurium

ABSTRACT Mycobacterium lepraemurium is the causative agent of murine leprosy, a chronic, granulomatous disease similar to human leprosy. Due to the similar clinical manifestations of human and murine leprosy and the difficulty of growing both bacilli axenically, Mycobacterium leprae and M. lepraemurium were once thought to be closely related, although it was later suggested that M. lepraemurium might be related to Mycobacterium avium. In this study, the complete genome of M. lepraemurium was sequenced using a combination of PacBio and Illumina sequencing. Phylogenomic analyses confirmed that M. lepraemurium is a distinct species within the M. avium complex (MAC). The M. lepraemurium genome is 4.05 Mb in length, which is considerably smaller than other MAC genomes, and it comprises 2,682 functional genes and 1,139 pseudogenes, which indicates that M. lepraemurium has undergone genome reduction. An error-prone repair homologue of the DNA polymerase III α-subunit was found to be nonfunctional in M. lepraemurium, which might contribute to pseudogene formation due to the accumulation of mutations in nonessential genes. M. lepraemurium has retained the functionality of several genes thought to influence virulence among members of the MAC. IMPORTANCE Mycobacterium lepraemurium seems to be evolving toward a minimal set of genes required for an obligatory intracellular lifestyle within its host, a niche seldom adopted by most mycobacteria, as they are free-living. M. lepraemurium could be used as a model to elucidate functions of genes shared with other members of the MAC. Its reduced gene set can be exploited for studying the essentiality of genes in related pathogenic species, which might lead to discovery of common virulence factors or clarify host-pathogen interactions. M. lepraemurium can be cultivated in vitro only under specific conditions and even then with difficulty. Elucidating the metabolic (in)capabilities of M. lepraemurium will help develop suitable axenic media and facilitate genetic studies. IMPORTANCE Mycobacterium lepraemurium seems to be evolving toward a minimal set of genes required for an obligatory intracellular lifestyle within its host, a niche seldom adopted by most mycobacteria, as they are free-living. M. lepraemurium could be used as a model to elucidate functions of genes shared with other members of the MAC. Its reduced gene set can be exploited for studying the essentiality of genes in related pathogenic species, which might lead to discovery of common virulence factors or clarify host-pathogen interactions. M. lepraemurium can be cultivated in vitro only under specific conditions and even then with difficulty. Elucidating the metabolic (in)capabilities of M. lepraemurium will help develop suitable axenic media and facilitate genetic studies.

scholarly journals Host Airway Proteins Interact with Staphylococcus aureus during Early Pneumonia

2008 ◽  
Vol 76 (3) ◽  
pp. 888-898 ◽  
Author(s):  
Christy L. Ventura ◽  
Roger Higdon ◽  
Eugene Kolker ◽  
Shawn J. Skerrett ◽  
Craig E. Rubens
Keyword(s):  
Staphylococcus Aureus ◽  
Shotgun Proteomics ◽  
Community Acquired Pneumonia ◽  
Host Proteins ◽  
Host Pathogen Interactions ◽  
Complement Components ◽  
Host Pathogen ◽  
Hospital Acquired

ABSTRACT Staphylococcus aureus is a major cause of hospital-acquired pneumonia and is emerging as an important etiological agent of community-acquired pneumonia. Little is known about the specific host-pathogen interactions that occur when S. aureus first enters the airway. A shotgun proteomics approach was utilized to identify the airway proteins associated with S. aureus during the first 6 h of infection. Host proteins eluted from bacteria recovered from the airways of mice 30 min or 6 h following intranasal inoculation under anesthesia were subjected to liquid chromatography and tandem mass spectrometry. A total of 513 host proteins were associated with S. aureus 30 min and/or 6 h postinoculation. A majority of the identified proteins were host cytosolic proteins, suggesting that S. aureus was rapidly internalized by phagocytes in the airway and that significant host cell lysis occurred during early infection. In addition, extracellular matrix and secreted proteins, including fibronectin, antimicrobial peptides, and complement components, were associated with S. aureus at both time points. The interaction of 12 host proteins shown to bind to S. aureus in vitro was demonstrated in vivo for the first time. The association of hemoglobin, which is thought to be the primary staphylococcal iron source during infection, with S. aureus in the airway was validated by immunoblotting. Thus, we used our recently developed S. aureus pneumonia model and shotgun proteomics to validate previous in vitro findings and to identify nearly 500 other proteins that interact with S. aureus in vivo. The data presented here provide novel insights into the host-pathogen interactions that occur when S. aureus enters the airway.

VI.Entamoeba histolytica: parasite-host interactions

2001 ◽  
Vol 280 (6) ◽  
pp. G1049-G1054 ◽  
Author(s):  
Samuel L. Stanley ◽  
Sharon L. Reed
Keyword(s):  
Virulence Factors ◽  
Host Response ◽  
Host Cells ◽  
Intestinal Epithelial ◽  
Small Peptides ◽  
In Vivo Models ◽  
Host Interactions ◽  
Models Of Disease

The protozoan intestinal parasite Entamoeba histolytica remains a significant cause of morbidity and mortality worldwide. E. histolytica causes two major clinical syndromes, amebic colitis and amebic liver abscess. Recent advances in the development of in vitro and in vivo models of disease, new genetic approaches, the identification of key E. histolytica virulence factors, and the recognition of crucial elements of the host response to infection have led to significant insights into the pathogenesis of amebic infection. E. histolytica virulence factors include 1) a surface galactose binding lectin that mediates E. histolyticabinding to host cells and may contribute to amebic resistance to complement, 2) amebapores, small peptides capable of lysing cells, which may play a role in killing intestinal epithelial cells, hepatocytes, and host defense cells, and 3) a family of secreted cysteine proteinases that play a key role in E. histolytica tissue invasion, evasion of host defenses, and parasite induction of gut inflammation. Amebae can both lyse host cells and induce their suicide through programmed cell death. The host response is also an important factor in the outcome of infection, and neutrophils may play a key role in contributing to the tissue damage seen in amebiasis and in controlling amebic infection.

DksA is a central regulatory switch for stress protection and virulence in Acinetobacter baumannii

2021 ◽  
Author(s):  
Ram Maharjan ◽  
Geraldine Sulivan ◽  
Felise Adams ◽  
Natasha Delgado ◽  
Lucie Semenec ◽  
...  
Keyword(s):  
Stress Response ◽  
Acinetobacter Baumannii ◽  
Galleria Mellonella ◽  
Resistance Mechanisms ◽  
Term Survival ◽  
In Vivo Models ◽  
Molecular Control ◽  
Stress Protection

Abstract Bacterial coordination of stress resistance mechanisms in harsh environments is key to long-term survival and evolutionary success. In many Gram-negative pathogens, both general- and specific-stress response are controlled by alternative sigma factors such as RpoS. The critically important pathogen Acinetobacter baumannii is notoriously recalcitrant to external stressors, yet it lacks RpoS, so the molecular control of its resilience remains unclear. Here, we used transposon insertion sequencing to characterize the molecular responses of Acinetobacter baumannii to two biologically-important metals stressors, zinc and copper, and discovered that the transcriptional regulator DksA acts as a major regulatory stress-protection switch. We mapped the highly pleiotropic nature of DksA using transcriptomics and phenomics and found that it controls ribosomal protein expression, metabolism of gluconeogenic substrates and survival in stresses that cause oxidative damage. A. baumannii strains lacking DksA were no longer virulent in both murine and Galleria mellonella in vivo models. In vitro, DksA mutants exhibited increased sensitivity to human serum and antibiotics yet promoted biofilm and capsule formation. Our study provides detailed insight into the unique role that DksA plays in stress protection and virulence for A. baumannii and lays the groundwork for understanding of RpoS-independent regulatory general stress response.

scholarly journals In vivo Fitness of Acinetobacter baumannii Strains in Murine Infection Is Associated with International Lineage II-rep-2 and International Lineage III Clones Showing High Case Fatality Rates in Human Infections

2020 ◽  
Vol 8 (6) ◽  
pp. 847
Author(s):  
Amir Nutman ◽  
Jonathan Lellouche ◽  
Ziv Lifshitz ◽  
Rivka Glick ◽  
Yehuda Carmeli
Keyword(s):  
Acinetobacter Baumannii ◽  
Case Fatality ◽  
Growth Curves ◽  
Thigh Muscle ◽  
Day Case ◽  
In Vivo Models ◽  
Carbapenem Resistant ◽  
Human Infections

We previously reported that the 14-day case fatality rate (CFR) in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia varied between infecting clones. Here, we evaluated the in vitro and in vivo fitness of CRAB blood isolates belonging to clones with low CFR (< 32% 14-day mortality) and high CFR (65% 14-day mortality). Fitness was measured in vitro using a growth curve assay and in vivo using murine thigh muscle and septicemia models of infection. Our sample included 38 CRAB isolates belonging to two clones with low CFR (international lineage (IL)-II-rep-1, n = 13 and IL-79, n = 6) and two clones with high CFR (IL-III, n = 9 and IL-II-rep-2, n = 10). In in vitro growth curves, mean lag time, generation time and maximal growth varied between clones but could not discriminate between the high and low CFR clones. In the in vivo models, bacterial burdens were higher in mice infected with high CFR clones than in those infected with low CFR clones: in thigh muscle, 8.78 ± 0.25 vs. 7.53 ± 0.25 log10CFU/g, p < 0.001; in infected spleen, 5.53 ± 0.38 vs. 3.71 ± 0.35 log10CFU/g, p < 0.001. The thigh muscle and septicemia model results were closely correlated (r = 0.93, p < 0.01). These results suggest that in vivo but not in vitro fitness is associated with high CFR clones.

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