Pertussis, commonly known as whooping cough, is attributable to the Gram-negative bacterium Bordetella pertussis. Vaccination options against B. pertussis include whole-cell pertussis (wP) and acellular pertussis (aP) vaccines. Acellular vaccines typically consist of purified proteins from B. pertussis, especially filamentous hemagglutinin (Fha), pertussis toxin (Ptx), and pertactin (Prn), and often include fimbrial proteins (Fim2 and Fim3). During the 1990s, several countries recommended substituting the less reactive aP vaccines for wP vaccines (1). In China, the National Immunization Program has been administering the diphtheria–tetanus–wP vaccine since the 1980s. A shift to the diphtheria–tetanus–aP (DTaP) vaccine, which incorporates Ptx, Prn and Fha as bioactive components, occurred between 2007 and 2013 (2).

The resurgence of pertussis poses a significant global public health challenge, primarily due to vaccine escape and antigenic shifts in Bordetella pertussis. There has been a noted divergence in the antigens of B. pertussis between the strains circulating in the population and those present in vaccines (3–4). Strains exhibiting a novel promoter for Ptx (ptxP3) have been identified in various countries, including China (5–7). Significant virulence factors such as Prn and Fha, both integral components of B. pertussis vaccines, have shown variations. The first report of Prn-deficient B. pertussis strains occurred in the USA in 1994 (4), with similar strains later identified in China in 2019 (8). Instances of Fha-deficient B. pertussis strains have also been documented. Additionally, there has been a rise in the occurrence of high-level macrolide-resistant B. pertussis strains, particularly in China since 2013, which is linked to the A2037G mutation in the 23S rRNA gene (5–6).

Since 2022, two Beijing-based sentinel hospitals have implemented a pertussis surveillance study, monitoring cases suspected of pertussis and conducting laboratory tests for B. pertussis using real-time PCR from January 2022 to December 2023. A total of 44 B. pertussis strains were isolated from nasopharyngeal swab specimens collected from 44 outpatients, consisting of 13 infants, 28 children, and 3 adults. These strains underwent genetic analysis through sequencing using the Illumina HiSeq 2500 system. This analysis focused on genes encoding eight vaccine-related antigens (ptxA, ptxC, ptxP3, prn, fim2, fim3, fhaB, and tcfA) and a type III secretion system gene (bscI), analyzed using BLAST with an E-value threshold of 1e−5. Allelic variations for ptxA, ptxC, ptxP3, prn, fim2-1, fim3-1, fhaB, tcfA2, and bscI were identified through comparison on the BIGSdb-Pasteur platform (https://bigsdb.pasteur.fr/cgi-bin/bigsdb/bigsdb.pl?db=pubmlst_bordetella_seqdef). All identified Bordetella pertussis strains shared the same antigenic profile: ptxA1, ptxC2, ptxP3, prn150, fim2-1, fim3-1, fhaB1, tcfA2, and bscI2. Notably, 14 strains had the prn150 allele located on the same DNA sequence contig, whereas in the remaining 30 strains, this allele was split across two contigs due to a gene disruption at a site 240 bp upstream from the prn start site, identified as a common Prn-deficiency mechanism (4). This disruption was characterized by a 6-bp (GCTAGA) overlap and was associated with a reversed insertion of IS481, hinted by a “CTAG” termination sequence (accession no. M22031)（Fig. 1）. This insertion’s location and orientation were confirmed by third-generation sequencing for two strains, one with an intact prn150 (BJSY2023BRK008) and one with a truncated prn150 (BJSY2022BRK001), performed on the PacBio platform. The completed genome of BJSY2022BRK001 confirmed reversed IS481 insertion in prn (Fig. 2). Additionally, two strains showed a Fha deficiency, evidenced by a deletion of a “G” at position 1087 in the homopolymeric G-tract of fhaB, a mutation previously documented for causing this deficiency (3).

Figure 1. 

Comparison of the disrupted prn gene with the complete prn150 allele, highlighting six overlapping bases (GCTAGA) between the contigs. OP866997-prn150: intact prn150.

Figure 2. 

Circularized genomes featuring complete and truncated prn150 genes. The purple ring denoted BJSY2023BRK008, while the light blue ring signified BJSY2022BRK001. The diagram illustrated the gene structures of complete prn150 and prn150 with a reversed IS481 insertion.

All Bordetella pertussis strains possessed identical 23S rRNA gene sequences and exhibited an A2037G mutation. Susceptibility testing conducted with E-test strips indicated that all strains were resistant to erythromycin and azithromycin, with minimum inhibitory concentrations (MIC) exceeding 256 μg/mL.

A phylogenetic tree was constructed based on core SNPs from 148 B. pertussis genomes. This set includes genomes from all strains analyzed in this study, two reference genomes (Tohama I, NC002929.2 and CS, CP086368), and an additional 102 genomes sourced from the NCBI database (BioProject no. PRJNA908268). The analysis revealed no specific linkage among the 44 isolated strains (Figure 3).

Figure 3. 

Phylogenetic tree based on core SNPs from Bordetella pertussis. The genome highlighted with a light blue background was sequenced in this study, and red fonts were Prn-deficient strains. Genomes marked with a red and green hexagon represented vaccine and Fha-deficient strains, respectively. The strains isolated during this study were distributed across various clusters within the tree.

Abbreviation: SNP=Single Nucleotide Polymorphism.

MIT researchers have developed a novel gas detection system that combines metal-organic frameworks with a durable polymer to enable continuous and sensitive monitoring of toxic gases like nitrogen dioxide. This new sensor can detect low

A breakthrough in gas detection technology at <span class="glossaryLink" aria-describedby="tt" data-cmtooltip="

” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>MIT combines high sensitivity and continuous monitoring. The material could be made as a thin coating to analyze air quality in industrial or home settings.

Most systems designed to detect toxic gases in industrial or domestic environments are limited to single or minimal uses. Researchers at MIT, however, have created a detector capable of providing continuous, low-cost monitoring of these gases.

The new system combines two existing technologies, bringing them together in a way that preserves the advantages of each while avoiding their limitations. The team used a material called a metal-organic framework, or MOF, which is highly sensitive to tiny traces of gas but whose performance quickly degrades, and combined it with a polymer material that is highly durable and easier to process, but much less sensitive.

The results are reported today in the journal Advanced Materials, in a paper by MIT professors Aristide Gumyusenge, Mircea Dinca, Heather Kulik, and Jesus del Alamo, graduate student Heejung Roh, and postdocs Dong-Ha Kim, Yeongsu Cho, and Young-Moo Jo.

Researchers at MIT have developed a detector that could provide continuous monitoring for the presence of toxic gases, at low cost. The team used a material called a metal-organic framework, or MOF (pictured as the black lattice), which is highly sensitive to tiny traces of gas but whose performance quickly degrades. They combined the MOF with a polymer material, shown as the teal translucent strands, that is highly durable but much less sensitive. Credit: Courtesy of the researchers

Innovative Material Combination

Highly porous and with large surface areas, <span class="glossaryLink" aria-describedby="tt" data-cmtooltip="

” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>MOFs come in a variety of compositions. Some can be insulators, but the ones used for this work are highly electrically conductive. With their sponge-like form, they are effective at capturing molecules of various gases, and the sizes of their pores can be tailored to make them selective for particular kinds of gases. “If you are using them as a sensor, you can recognize if the gas is there if it has an effect on the resistivity of the MOF,” says Gumyusenge, the paper’s senior author and the Merton C. Flemings Career Development Assistant Professor of Materials Science and Engineering.

The drawback for these materials’ use as detectors for gases is that they readily become saturated, and then can no longer detect and quantify new inputs. “That’s not what you want. You want to be able to detect and reuse,” Gumyusenge says. “So, we decided to use a polymer composite to achieve this reversibility.”

The team used a class of conductive polymers that Gumyusenge and his co-workers had previously shown can respond to gases without permanently binding to them. “The polymer, even though it doesn’t have the high surface area that the MOFs do, will at least provide this recognize-and-release type of phenomenon,” he says.

Researchers demonstrated the material’s ability to detect nitrous oxide, a toxic gas produced by many kinds of combustion, in a small lab-scale device. After 100 cycles of detection, the material was still maintaining its baseline performance within a margin of about 5 to 10 percent, demonstrating its long-term use potential. Here is the layout of the sensing setup. Credit: Courtesy of the researchers

Enhanced Sensing Capabilities

The team combined the polymers in a liquid solution along with the MOF material in powdered form, and deposited the mixture on a substrate, where they dry into a uniform, thin coating. By combining the polymer, with its quick detection capability, and the more sensitive MOFs, in a one-to-one ratio, he says, “suddenly we get a sensor that has both the high sensitivity we get from the MOF and the reversibility that is enabled by the presence of the polymer.”

The material changes its electrical resistance when molecules of the gas are temporarily trapped in the material. These changes in resistance can be continuously monitored by simply attaching an ohmmeter to track the resistance over time. Gumyusenge and his students demonstrated the composite material’s ability to detect nitrogen dioxide, a toxic gas produced by many kinds of combustion, in a small lab-scale device. After 100 cycles of detection, the material was still maintaining its baseline performance within a margin of about 5 to 10 percent, demonstrating its long-term use potential.

In addition, this material has far greater sensitivity than most presently used detectors for nitrogen dioxide, the team reports. This gas is often detected after the use of stove ovens. And, with this gas recently linked to many asthma cases in the U.S., reliable detection in low concentrations is important. The team demonstrated that this new composite could detect, reversibly, the gas at concentrations as low as 2 parts per million.

Applications and Future Directions

While their demonstration was specifically aimed at nitrogen dioxide, Gumyusenge says, “We can definitely tailor the chemistry to target other volatile molecules,” as long as they are small polar analytes, “which tend to be most of the toxic gases.”

Besides being compatible with a simple hand-held detector or a smoke-alarm type of device, one advantage of the material is that the polymer allows it to be deposited as an extremely thin uniform film, unlike regular MOFs, which are generally in an inefficient powder form. Because the films are so thin, there is little material needed and production material costs could be low; the processing methods could be typical of those used for industrial coating processes. “So, maybe the limiting factor will be scaling up the synthesis of the polymers, which we’ve been synthesizing in small amounts,” Gumyusenge says.

“The next steps will be to evaluate these in real-life settings,” he says. For example, the material could be applied as a coating on chimneys or exhaust pipes to continuously monitor gases through readings from an attached resistance monitoring device. In such settings, he says, “we need tests to check if we truly differentiate it from other potential contaminants that we might have overlooked in the lab setting. Let’s put the sensors out in real-world scenarios and see how they do.”

Reference: “Robust Chemiresistive Behavior in Conductive Polymer/MOF Composites” by Heejung Roh, Dong-Ha Kim, Yeongsu Cho, Young-Moo Jo, Jesús A. del Alamo, Heather J. Kulik, Mircea Dincă and Aristide Gumyusenge, 17 April 2024, Advanced Materials.
DOI: 10.1002/adma.202312382

The work was supported by the MIT Climate and Sustainability Consortium (MCSC), the Abdul Latif Jameel Water and Food Systems Lab (J-WAFS) at MIT, and the U.S. Department of Energy.

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