Mannose-modified chitosan microspheres enhance OprF-OprI-mediated protection of mice against Pseudomonas aeruginosa infection via induction of mucosal immunity

Cui, Ziyin; Han, Dongyi; Sun, Xiaoyu; Zhang, Mingliang; Feng, Xin; Sun, Changjiang; Gu, Jingmin; Tong, Chuan; Lei, Liancheng; Wang, Han

doi:10.1007/s00253-014-6147-z

Cited by 28 publications

(25 citation statements)

References 66 publications

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“…7 No data are available. 8 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 overnight together with sewage samples in LB broth at 37 C as previously described [13]. The culture was centrifuged...…”

Section: Phage Isolation and Purificationmentioning

confidence: 97%

“…Mice were euthanized at 24 h after the P. aeruginosa strain D9 challenge, and the lungs were removed and immediately placed in 4% formalin. The formalin-fixed tissues were processed, stained with hematoxylin and eosin and then analyzed by microscopy [8].…”

Section: Phage Therapy In the Murine Hemorrhagic Pneumonia Modelmentioning

confidence: 99%

“…P. aeruginosa is a common Gram-negative opportunistic pathogen that is widely present in a variety of environments. P. aeruginosa causes acute, life-threatening or chronic infections in patients with cystic fibrosis (CF) or severe burns, and in patients who are immunosuppressed [8]. In animals, P. aeruginosa causes endometritis in horses [21], mastitis in cows and other ruminant animals [29], otitis media and otitis interna in chinchillas [18].…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic effect of the YH6 phage in a murine hemorrhagic pneumonia model

Yang

Gong

et al. 2015

Research in Microbiology

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Section: Phage Isolation and Purificationmentioning

confidence: 97%

Section: Phage Therapy In the Murine Hemorrhagic Pneumonia Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Therapeutic effect of the YH6 phage in a murine hemorrhagic pneumonia model

Yang

Gong

et al. 2015

Research in Microbiology

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“…Three mice in each group (n ϭ 6) were euthanized at 24 h after the USA300 challenge, and the lungs of these mice were removed and immediately placed in 4% formalin. The formalin-fixed tissues were processed and stained with hematoxylin and eosin (H&E) using a routine staining procedure and then analyzed by microscopy (35). The ratio of wet lung tissue to dry lung tissue (W/D ratio) was also calculated.…”

Section: Methodsmentioning

confidence: 99%

Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus

Xia

Wang

et al. 2016

Appl Environ Microbiol

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c Pneumonia is one of the most prevalent Staphylococcus aureus-mediated diseases, and the treatment of this infection is becoming challenging due to the emergence of multidrug-resistant S. aureus, especially methicillin-resistant S. aureus (MRSA) strains. It has been reported that LysGH15, the lysin derived from phage GH15, displays high efficiency and a broad lytic spectrum against MRSA and that apigenin can markedly diminish the alpha-hemolysin of S. aureus. In this study, the combination therapy of LysGH15 and apigenin was evaluated in vitro and in a mouse S. aureus pneumonia model. No mutual adverse influence was detected between LysGH15 and apigenin in vitro. In animal experiments, the combination therapy showed a more effective treatment effect than LysGH15 or apigenin monotherapy (P < 0.05). The bacterial load in the lungs of mice administered the combination therapy was 1.5 log units within 24 h after challenge, whereas the loads in unprotected mice or mice treated with apigenin or LysGH15 alone were 10.2, 4.7, and 2.6 log units, respectively. The combination therapy group showed the best health status, the lowest ratio of wet tissue to dry tissue of the lungs, the smallest amount of total protein and cells in the lung, the fewest pathological manifestations, and the lowest cytokine level compared with the other groups (P < 0.05). With regard to its better protective efficacy, the combination therapy of LysGH15 and apigenin exhibits therapeutic potential for treating pneumonia caused by MRSA. This paper reports the combination therapy of lysin and natural products derived from traditional Chinese medicine. Staphylococcus aureus is a ubiquitous and zoonotic pathogen that causes high morbidity and mortality in a variety of diseases, ranging from skin and soft tissue infections to necrotizing pneumonia and overwhelming sepsis (1, 2). S. aureus pneumonia is one of the most prevalent S. aureus-mediated diseases and accounts for 13.3% of all invasive S. aureus infections (3). Treatment of S. aureus infection has become increasingly difficult, given the prevalence of multidrug-resistant S. aureus strains, especially the widespread existence of methicillin-resistant S. aureus (MRSA) strains (4). MRSA strains are typically resistant to multiple antibiotics, including gentamicin, erythromycin, fluoroquinolones, and ofloxacin, among others (5). There are also reports of vancomycin-resistant S. aureus (VRSA), raising serious concerns within the medical community (6-8). Therefore, there is an urgent need for novel therapeutic strategies that are efficient against this pathogen.Lysin, which is encoded by the phage (bacterial virus) genome at the end of the phage lytic life cycle to lyse the host cell, can rapidly and specifically lyse Gram-positive bacteria when exogenously applied (9). Because the bacterial cell wall is conserved and necessary for the life cycle, the current lack of bacterial resistance against lysin is not surprising (10). In addition, its species specificity or type specificity ensures that lysin w...

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“…Vaccination is a feasible strategy for preventing P. aeruginosa infections . However, development of vaccines against P. aeruginosa has been hindered by the wide phenotypic variation among its serotypes .…”

mentioning

confidence: 99%

Salmonella Typhimurium strain expressing OprF‐OprI protects mice against fatal infection by Pseudomonas aeruginosa

Zhang¹,

Sun²,

Gu³

et al. 2015

Microbiology and Immunology

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Pseudomonas aeruginosa poses a major threat to human health and to the mink industry. Thus, development of vaccines that elicit robust humoral and cellular immunity against P. aeruginosa is greatly needed. In this study, a recombinant attenuated Salmonella vaccine (RASV) that expresses the outer membrane proteins fusion OprF 190-342 -OprI 21-83 (F1I2) from P. aeruginosa was constructed and the potency of this vaccine candidate assessed by measuring F1I2-specific humoral immune responses upon vaccination through s.c. or oral routes. S.C. administration achieved higher serum IgG titers and IgA titers in the intestine and induced stronger F1I2-specific IgG and IgA titers in lung homogenate than did oral administration, which resulted in low IgG titers and no local IgA production. High titers of IFN-g, IL-4, and T-lymphocyte subsets induced a mixed Th1/Th2 response in mice immunized s.c., indicating elicitation of cellular immunity. Importantly, when immunized mice were challenged with P. aeruginosa by the intranasal route 30 days after the initial immunization, s.c. vaccination achieved 77.78% protection, in contrast to 41.18% via oral administration and 66.67% via Escherichia coli-expressed F1I2 (His-F1I2) vaccination. These results indicate that s.c. vaccination provides a better protective response against P. aeruginosa infection than do oral administration and the His-F1I2 vaccine.Key words outer membrane protein, Pseudomonas aeruginosa, Salmonella Typhimurium, subcutaneous vaccination.Pseudomonas aeruginosa is a major cause of pulmonary infection, causing cystic fibrosis-and non-cystic fibrosisrelated bronchiectasis and chronic obstructive pulmonary disease. It is also a common pathogen responsible for hospital-acquired infections in burn, transplant, cancer and intensive care unit patients (1). Various animals, including dogs, dairy cows, horses, mink and foxes, are believed to be susceptible to P. aeruginosa (2). In particular, P. aeruginosa has been a major cause of hemorrhagic pneumonia in mink for the last 50 years, resulting in serious losses in the Chinese mink industry (2, 3). Although there have been considerable advances in antimicrobial therapy for the treatment and control of P. aeruginosa infection, undesirable adverse effects remain a persistent problem, primarily because of the natural resistance of this pathogen and its formidable ability to acquire resistance to multiple antimicrobial agents by various mechanisms. Therefore, measures to effectively contain P. aeruginosa infection are urgently needed. List of Abbreviations: APC, antigen-presenting cell; DAP, 2,6-diaminopimelic acid; DTH, delayed-type hypersensitivity; F1, part of outer membrane proteins F ) of Pseudomonas aeruginosa; I2, part of outer membrane proteins I (OprI 21-83 ) of Pseudomonas aeruginosa; PQ, Salmonella Typhimurium LH430 with asd deleted; RASV, recombinant attenuated Salmonella vaccine.

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Mannose-modified chitosan microspheres enhance OprF-OprI-mediated protection of mice against Pseudomonas aeruginosa infection via induction of mucosal immunity

Cited by 28 publications

References 66 publications

Therapeutic effect of the YH6 phage in a murine hemorrhagic pneumonia model

Therapeutic effect of the YH6 phage in a murine hemorrhagic pneumonia model

Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus

Salmonella Typhimurium strain expressing OprF‐OprI protects mice against fatal infection by Pseudomonas aeruginosa

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