Comparative Genomics of Aeromonas hydrophila Secretion Systems and Mutational Analysis of hcp1 and vgrG1 Genes From T6SS

Tekedar, Hasan C.; Abdelhamed, Hossam; Kumru, Salih; Blom, Jochen; Karsi, Attila; Lawrence, Mark L.

doi:10.3389/fmicb.2018.03216

Cited by 23 publications

(28 citation statements)

References 99 publications

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“…Remarkably, these remnant genes that code T6SS virulence-associated effector proteins, Hcp1 (hemolysin co-regulated protein) and VgrG (valine-glycine repeat G), appear to contribute to vAh pathogenicity. Despite the apparent lack of a functional T6SS, deletion of hcp1 or vgrG genes from vAh ML09-119, the same strain used in these studies, resulted in a significant attenuation of virulence in catfish when challenged by immersion (10). These data suggest that these proteins may be exported by an alternative secretory mechanism in the vAh pathotype.…”

Section: Introductionmentioning

confidence: 82%

“…Furthermore, T2SS substrates are generally highly stable in the environment, as evidenced by their presence in many extremophiles (17). While T2SS are widespread in A. hydrophila (10), the presence of a T3SS or T6SS has been generally considered more important for virulence (9) and, in some cases, essential to the infectious process (18,19). Both T3SS and T6SS rely on needle-like "injectisomes" to mediate effector molecules directly from the bacterial cytoplasm into the target host cell (20,21), while T2SS substrates are released from the periplasm through the outer membrane, in a seemingly indiscriminate manner, into the extracellular milieu (17).…”

Section: Introductionmentioning

confidence: 99%

“…Both T3SS and T6SS rely on needle-like "injectisomes" to mediate effector molecules directly from the bacterial cytoplasm into the target host cell (20,21), while T2SS substrates are released from the periplasm through the outer membrane, in a seemingly indiscriminate manner, into the extracellular milieu (17). Interestingly, genomic comparisons of secretion systems in vAh strains found all 27 lacked a T3SS, and 18 of the 27 isolates, including all U.S. isolates of the ML09-119 pathotype, lacked a complete T6SS, though all vAh genomes contained at least three genes from the T6SS cluster (10). Remarkably, these remnant genes that code T6SS virulence-associated effector proteins, Hcp1 (hemolysin co-regulated protein) and VgrG (valine-glycine repeat G), appear to contribute to vAh pathogenicity.…”

Section: Introductionmentioning

confidence: 99%

“…These data suggest that these proteins may be exported by an alternative secretory mechanism in the vAh pathotype. The majority of Chinese vAh isolates possess a complete T6SS (10) and in these isolates the T6SS appears to play important roles in bacterial virulence, particularly for biofilm formation (22). In 2014, a second U.S. vAh pathovar containing a complete T6SS (S14-452) was isolated from diseased fish in Mississippi (23).…”

Section: Introductionmentioning

confidence: 99%

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Type II Secretion Is Essential for Virulence of the Emerging Fish Pathogen, Hypervirulent Aeromonas hydrophila

2020

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Hypervirulent Aeromonas hydrophila (vAh) is an emerging pathogen in freshwater aquaculture systems. In the U.S.A., outbreaks of motile aeromonad septicemia associated with vAh result in the loss of over 3 million pounds of channel catfish from Southeastern production systems each year. A. hydrophila is a well-known opportunistic pathogen that secretes degradative and potentially toxigenic proteins, and the rapid mortality that occurs when catfish are challenged with vAh by intraperitoneal injection suggests that vAh-induced motile aeromonad septicemia may be, in part, a toxin-mediated disease. While vAh isolates from carp isolated in China possess complete Type I, Type II, and Type VI secretion systems, many of the US catfish isolates only possess complete Type I and Type II secretions systems. In order to determine the role of secreted proteins in vAh-induced disease, and to determine the extent of protein secretion by the Type II secretion pathway, an exeD secretin mutant was constructed using a recombineering method in the well-characterized US vAh strain, ML09-119. Wild-type and mutant secretomes were analyzed for protein content by SDS-PAGE and by assays for specific enzymes and toxins. Type II secretion-deficient mutants had a near complete loss of secreted proteins and enzyme/toxin activity, including hemolytic and proteolytic activity. The intact Type II secretion system was cloned and used to complement the deletion mutant, ML09-119 exeD, which restored protein secretion and the degradative and toxigenic potential. In vivo challenges in channel catfish resulted in complete attenuation of virulence in ML09-119 exeD, while the complemented mutant was observed to have restored virulence. These results indicate that secreted proteins are critical to vAh virulence, and that the Type II secretion system is the primary secretory pathway utilized for multiple effectors of vAh pathogenesis.

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Section: Introductionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Type II Secretion Is Essential for Virulence of the Emerging Fish Pathogen, Hypervirulent Aeromonas hydrophila

2020

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“…Recent analysis of the hcp1 and vgrG1 genes from T6SS has demonstrated that their deletion from a virulent A. hydrophila isolate leads to reduction of their virulence (approx. 2-fold) in relation to the parent strain (Tekedar et al, 2018). This proves a significant contribution of these genes in the Aeromonas virulence potential.…”

Section: Secretion Systemmentioning

confidence: 58%

Role of Bacterial Secretion Systems and Effector Proteins – Insight into the Pathogenicity Mechanisms in Aeromonas

2020

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Gram-negative bacteria have developed several nanomachine channels known as type II, III, IV and VI secretion systems that enable export of effector proteins/toxins from the cytosol across the outer membrane to target host cells. Protein secretion systems are critical to bacterial virulence and interactions with other organisms. Aeromonas utilize various secretion machines e.g. two-step T2SS, a Sec-dependent system as well as one-step, Sec-independent T3SS and T6SS systems to transport effector proteins/toxins and virulence factors. Type III secretion system (T3SS) is considered the dominant virulence system in Aeromonas. The activity of bacterial T3SS effector proteins most often leads to disorders in signalling pathways and reorganization of the cell cytoskeleton. There are also scientific reports on the pathogenicity mechanism associated with host cell apopotosis/pyroptosis resulting from secretion of a cytotoxic enterotoxin, i.e. the Act protein, by the T2SS secretion system and an effector protein Hcp by the T6SS system. Type IV secretion system (T4SS) is the system which translocate protein substrates, protein-DNA complexes and DNA into eukaryotic or bacterial target cells. In this paper, the contribution of virulence determinants involved in the pathogenicity potential of Aeromonas is discussed. Considering that the variable expression of virulence factors has a decisive impact on the differences observed in the virulence of particular species of microorganisms, it is important to assess the correlation between bacterial pathogenicity and their virulence-associated genes.

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Antimicrobial resistance in aeromonads and new therapies targeting quorum sensing

Neil,

Cheney,

Rosenzweig

et al. 2024

Appl Microbiol Biotechnol

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Aeromonas species (spp.) are well-known fish pathogens, several of which have been recognized as emerging human pathogens. The organism is capable of causing a wide spectrum of diseases in humans, ranging from gastroenteritis, wound infections, and septicemia to devastating necrotizing fasciitis. The systemic form of infection is often fatal, particularly in patients with underlying chronic diseases. Indeed, recent trends demonstrate rising numbers of hospital-acquired Aeromonas infections, especially in immuno-compromised individuals. Additionally, Aeromonas-associated antibiotic resistance is an increasing challenge in combating both fish and human infections. The acquisition of antibiotic resistance is related to Aeromonas’ innate transformative properties including its ability to share plasmids and integron-related gene cassettes between species and with the environment. As a result, alternatives to antibiotic treatments are desperately needed. In that vein, many treatments have been proposed and studied extensively in the fish-farming industry, including treatments that target Aeromonas quorum sensing. In this review, we discuss current strategies targeting quorum sensing inhibition and propose that such studies empower the development of novel chemotherapeutic approaches to combat drug-resistant Aeromonas spp. infections in humans. Key points • Aeromonas notoriously acquires and maintains antimicrobial resistance, making treatment options limited. • Quorum sensing is an essential virulence mechanism in Aeromonas infections. • Inhibiting quorum sensing can be an effective strategy in combating Aeromonas infections in animals and humans.

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Comparative Genomics of Aeromonas hydrophila Secretion Systems and Mutational Analysis of hcp1 and vgrG1 Genes From T6SS

Cited by 23 publications

References 99 publications

Type II Secretion Is Essential for Virulence of the Emerging Fish Pathogen, Hypervirulent Aeromonas hydrophila

Type II Secretion Is Essential for Virulence of the Emerging Fish Pathogen, Hypervirulent Aeromonas hydrophila

Role of Bacterial Secretion Systems and Effector Proteins – Insight into the Pathogenicity Mechanisms in Aeromonas

Antimicrobial resistance in aeromonads and new therapies targeting quorum sensing

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